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γ-Tocotrienol (γ-T3) is a major subtype of vitamin E, mainly extracted from palm trees, barley, walnuts, and other plants. γ-T3 has effects on anti-inflammation, anti-oxidation, and potential chemoprevention against malignancies. It is still uncompleted to understand the effect of γ-T3 on the inhibitory mechanism of cancer. This study aimed to investigate whether γ-T3 enhanced autophagy in gastric cancer and the underlying molecular mechanism. The results showed that γ-T3 (0-90 μmol/L) inhibited the proliferation of gastric cancer MKN45 cells and AGS cells, and arrested the cell cycle at the G0/G1 phase in a dose-dependent manner. Autophagy was increased in MKN45 cells treated with γ-T3 (0-45 μmol/L), especially at a dose of 30 μmol/L for 24 h. These effects were reversed by 3-methyladenine pretreatment. Furthermore, γ-T3 (30 μmol/L) also significantly downregulated the expression of pGSK-3β (ser9) and β-catenin protein in MKN45 cells, and γ-T3 (20 mg/kg b.w.) effectively decreased the growth of MKN45 cell xenografts in BABL/c mice. GSK-3β inhibitor-CHIR-99021 reversed the negative regulation of GSK-3β/β-Catenin signaling and autophagy. Our findings indicated that γ-T3 enhances autophagy in gastric cancer cells mediated by GSK-3β/β-Catenin signaling, which provides new insights into the role of γ-T3 enhancing autophagy in gastric cancer., (© 2024 Wiley Periodicals LLC.)

5-Fluorouracil (5-FU) is widely used in the treatment of gastric cancer, and the emergence of drug resistance and toxic effects has limited its application. Therefore, there is an urgent need for safe and effective novel drugs or new therapies. β-Ionone (BI) is found in vegetables and fruits and possesses an inhibitory proliferation of tumor cells in vitro and in vivo. In this study, we investigated whether BI could enhance the inhibitory effects of 5-FU on the proliferation of gastric adenocarcinoma cells and the growth of gastric cancer cell xenografts in a mouse model. The effects of BI and 5-FU alone or their combination on the cell viability, apoptosis, and mitochondrial membrane potential, the cell cycle, and its related proteins-Cyclin D1, and CDK4 as well as PCNA and GSK-3β were evaluated in SGC-7901 cells and MKN45 cells by MTT, MB, flow cytometry and Western blot. In addition, the effects of BI and 5-FU alone or their combination on the growth of SGC-7901 cell xenografts in nude mice were investigated. The results showed that BI significantly enhanced the sensitivity of gastric adenocarcinoma cells to 5-FU in vitro and in vivo, i.e. proliferation inhibited, apoptosis induced and GSK-3β protein activated. Therefore, our results suggest that BI increases the antitumor effect of 5-FU on gastric adenocarcinoma cells, at least partly from an activated GSK-3β signaling pathway., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA., Methods: A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan-Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA., Results: There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P < 0.001). Univariate analysis showed that survival was related to sex, age, tumor stage, and N stage (P < 0.001 for all). Cox regression model analysis revealed that thoracoabdominal approach (P < 0.001) and transabdominal approach (P < 0.001) were significant risk factors for poor survival. GCA patients treated with the transthoracic approach had the best survival (5-year survival rate of 53.7%), and survival varied among the different surgical approaches for different tumor stages., Conclusion: Thoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary., (© 2022. The Author(s).)

Background: The microRNA plays an important role in tumor progression. MiR-1236-3p acts as a tumor suppressor in various malignancies., Objective: The aim of present study was to explore the expression of miR-1236-3p in gastric cancer (GC) and its correlation with clinicopathological features, and evaluate the feasibility of using it as a prognostic biomarker in GC., Methods: Seventy-six pairs of tissue specimens were collected from GC patients. MiR-1236-3p expression level was detected by using qRT-PCR. The diagnostic value of miR-1236-3p was evaluated by receiver operating characteristic curve, and Kaplan-Meier method was used to analyze the overall survival. Prognosis analysis was performed using multivariate cox proportional hazards regression analysis., Results: The expression of miR-1236-3p was significantly reduced in tumor tissues (P< 0.001). In addition, miR-1236-3p expression was correlated with TNM stage (P= 0.001), lymph node metastasis (P= 0.005) and differentiated degree (P= 0.001). The area under the curve was 0.7016, and its specificity and sensitivity were 60.53% and 73.68%. Kaplan-Meier survival curves showed that patients with high miR-1236-3p expression had better overall survival than those with low expression (P= 0.0190). Multivariate Cox regression analysis showed that the miR-1236-3p expression (P= 0.033) was an independent prognostic factor for overall survival of GC prognosis., Conclusions: The study showed that miR-1236-3p is downregulated in GC tissues, and low expression of miR-1236-3p is associated with a poor prognosis in GC. It may be a new diagnostic and prognostic biomarker for GC.

Background: Despite its rarity, studies have shown the incidence of gastric neuroendocrine tumors (G-NETs) is increasing. This study investigated the risk factors affecting the survival of G-NETs patients and their prognosis over time., Method: A retrospective analysis of 506 G-NETs patients who underwent surgery for nonmetastatic disease from the Surveillance, Epidemiology and End Result database from 1988 to 2011 was conducted. Multivariate Cox regression analyses identified the prognostic factors affecting overall survival (OS) and disease-specific survival (DSS). Three-year conditional survival (COS3 and CDS3) estimates at "x" year after treatment were calculated as follows: COS3 = OS(x + 3)/OS(x) and CDS3 = DSS(x + 3)/DSS(x)., Results: The 1-, 3-, and 5-year OS rates of all patients after surgery were 90.2%, 77.3%, and 68.8%, respectively. The 1-, 3-, and 5-year DSS rates after surgery were 93.9%, 84.5%, and 80.9%, respectively. In the multivariate analysis, age, tumor grade, and T stage were independent prognostic factors of OS and DSS (all P < 0.05). With 1-, 3-, and 5-year survivorship, the COS3 improved by +5.2 (82.2%), +7.2 (84.4%), and +8.5 (85.5%), respectively, and the CDS3 improved by +4.4 (89.4%), +9.1 (94.1%), and +12.5 (97.5%), respectively. Notably, the CDS3 improved dramatically among patients with advanced stage disease (eg, N0 stage: 93.0%-98.9%, Δ5.9% vs N1 stage: 52.0%-95.7%, Δ43.7%)., Conclusion: For G-NETs patients, age, tumor grade, T stage, and N stage were the clinicopathological factors significantly associated with prognosis. There were excellent outcomes for most G-NETs patients, with a CDS3 of greater than 90% across all independent prognostic factors after 5 years of survival., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The aim of this study was to compare the efficacies of the XELOX and DOS regimens as preoperative chemotherapy in patients with locally advanced gastric cancer., Methods: All cases of locally advanced gastric cancer treated with the XELOX or DOS regimen were reviewed retrospectively. Propensity score matching (PSM) was carried out to reduce selection bias based on age, gender, location, Lauren type, carcinoembryonic antigen level, clinical tumor stage, and clinical node stage., Results: From January 2010 to December 2016, 248 patients were matched; 159 of them received the XELOX regimen and 89 the DOS regimen. The response rates in the XELOX and DOS groups were 34.5 and 38.1%, respectively (P = 0.823). After four cycles of chemotherapy, 111 patients (69.8%) in the XELOX group and 65 patients (73.0%) in the DOS group underwent radical surgery (P = 0.485). The median progression-free survival (33.0 months vs. 18.7 months, P = 0.0356) and the median overall survival (43.8 months vs. 29.1 months, P = 0.0003) were longer for patients who received the DOS regimen than for those who received the XELOX regimen. The occurrence of grade 3 to 4 toxicity was similar in the two groups., Conclusions: For locally advanced gastric cancer patients, the DOS regimen showed more benefit than the XELOX regimen as preoperative chemotherapy, without any added toxicity effects.

Purpose We assessed the effectiveness of EOX (capecitabine, oxaliplatin and epirubicin) compared with XELOX (capecitabine and oxaliplatin) as preoperative chemotherapy for initially unresectable locally advanced gastric cancer.Methods This is a prospective observational study. Patients with unresectable locally advanced gastric cancer were performed EOX regimen or XELOX regimen at the discretion of the investigators. They were assessed for response every 2 cycles by CT (computed tomography) scan. A multidisciplinary team reassessed resectability after 4 cycles. The primary endpoint was the response rate. Secondary end points included the R0 resection rate, survival and adverse events.Results From November 2008 to May 2015, 242 patients were enrolled; 112 of them were assigned to EOX regimen and 130 to XELOX regimen. The response rates were 33.0% and 33.8% respectively in EOX group and XELOX group (P = 0.997). After 4 cycles of chemotherapy, 63 patients (56.3%) in EOX group and 81 patients (62.3%) in XELOX group received radical operation (P = 0.408). There was no significant difference in progress-free survival (PFS, 12.0m vs. 15.4m, P = 0.925) and overall survival (OS, 25.7m vs. 29.0m, P = 0.783) in two groups. In addition, more adverse effects occurred in EOX group, such as more leucopenia (22.3% vs. 10.0%, P = 0.014), neutropenia (23.2% vs. 11.5%, P = 0.025), fatigue (11.6% vs. 3.8%, P = 0.041) and vomiting (10.7% vs. 2.3%, P = 0.015).Conclusions For unresectable locally advanced gastric cancer patients, XELOX regimen showed similar effects in response rate, radical resection rate and survival benefits, but with less toxicity effects.

Background: Cases of primary gastric adenocarcinoma with metastasis to the breast are extremely rare. Till now, only 38 cases have been reported in PubMed since 1908., Case Presentation: We herein reported a race case of gastric adenocarcinoma with metastasis to the right breast. Breast biopsy showed invasive signet-ring cell breast carcinoma in the right breast. She was given a TEC regimen (docetaxel 75 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 600 mg/m(2) every 3 weeks) for one cycle but showed no objective response. Upper gastrointestinal endoscopy demonstrated an ulcerative mass in the gastric body. Biopsy demonstrated low-grade gastric adenocarcinoma with signet-ring features. In immunohistochemistry, mammary malignant cells were positive for cytokeratin 7, cytokeratin 20, villin, and ErbB2/HER2, but negative for gross cystic disease fluid protein-15, estrogen receptor, and progesterone receptor. The diagnosis of metastatic poorly differentiated signet-ring cell adenocarcinoma of the right breast identical to gastric primary was confirmed finally., Conclusions: Gastric cancer with metastasis to the breast can be diagnosed by clinical history, histological findings, and immunohistochemical markers.

Acute acalculous cholecystitis (AAC) is a rare complication of gastric surgery. The most commonly accepted concepts regarding its pathogenesis are bile stasis, sepsis and ischemia, but it has not been well described how to identify and manage this disease in the early stage. We report three cases of AAC in elderly patients immediately after gastric surgery, which were treated with three different strategies. One patient died 42 d after emergency cholecystectomy, and the other two finally recovered through timely cholecystostomy and percutaneous transhepatic gallbladder drainage, respectively. These cases informed us of the value of early diagnosis and proper treatment for perioperative AAC after gastric surgery. We further reviewed reported cases of AAC immediately after gastric operation, which may expand our knowledge of this disease.

Objective: To evaluate the clinicopathological features and prognosis of chronic gastric ulcer with early canceration in order to provide useful information for diagnosis and treatment strategies., Methods: A retrospective review of clinical data and prognosis from 43 patients of chronic gastric ulcer with early canceration from 2003 to 2010 was conducted. These data were compared with those with primary intra-mucosa gastric cancer (type I and II 275 cases, type III 68 cases)., Results: In 43 cases of chronic gastric ulcer with early canceration, 30 cases (69.8%) were male, 22 cases (51.2%) were younger than 60 years old. Lesions located in the body or antrum of the stomach in 39 cases (90.7%), were less than 2 cm in 26 cases (60.5%), were undifferentiated type in 23 cases (53.5%), and developed lymph node metastasis in 4 cases (9.3%). Lesions of 4 cases of chronic gastric ulcer with early canceration located in the upper third of the stomach, while those of type III primary intra-mucosal gastric cancer all located in the lower two thirds, and the difference was statistically significant (P<0.01). Compared to type III and type I and II primary intra-mucosal gastric cancer, chronic gastric ulcer with early canceration did not differ in clinicopathological characteristics such as histological type, vascular or lymphatic invasion, and lymph nodes metastasis (all P>0.05). The median follow-up time was 57 months (range 16 to 98 months). The 5-year overall survival was 95.3% in chronic gastric ulcer with early canceration group, similar to that of type I, II (97.4%) or type III (94.5%) primary intra-mucosal gastric cancer group (P>0.05)., Conclusions: The clinicopathological features of chronic gastric ulcer with early canceration are similar to those of primary intra-mucosal gastric cancer. The prognosis is promising for those patients undergoing surgical treatment.

Aim: To investigate the association between the CpG island methylator phenotype (CIMP) and serum Helicobacter pylori (H. pylori) levels for clinical prediction of gastric cancer (GC) progression., Methods: We analyzed the serum CIMP status of 75 patients with GC using a methylation marker panel and a methylation-specific polymerase chain reaction. Serum samples from 40 healthy persons were examined at the same time. The genes examined were APC, WIF-1, RUNX-3, DLC-1, SFRP-1, DKK and E-cad. H. pylori infection in serum was assayed with an anti-H. pylori immunoglobulin G antibody test and a rapid urease test., Results: The frequencies of high-level methylation in GC tissues for the seven genes were: 48% for APC, 57.33% for WIF-1, 56% for RUNX-3, 50.67% for DLC-1, 52% for SFRP-1, 54.67% for DKK, and 48% for E-cad. The frequencies in GC serum were 30.67% for APC, 34.67% for WIF-1, 37.33% for RUNX-3, 29.33% for DLC-1, 33.33% for SFRP-1, 32% for DKK, and 26.67% for E-cad. CIMP+ (defined as ≥ 3 methylated genes) was associated with 47 (62.67%) GC tissue samples and 44 (58.67%) GC serum samples. CIMP+ was not associated with non-neoplastic mucosal tissues or the serum of healthy persons. Of the 75 GC cases, 51 (68%) were H. pylori+, and 24 (32%) were H. pylori-. Of the 51 H. pylori+ cases, 36 were CIMP+ and 15 were CIMP-. In contrast, for the 24 H. pylori- cases, 11 were CIMP+, and 13 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ(2) = 4.27, P < 0.05). Of the 51 H. pylori+ GC patients, 34 were CIMP+ and 17 were CIMP-, while among the 24 H. pylori- GC cases, 10 were CIMP+ and 14 were CIMP-. The difference was significant between the H. pylori+ and H. pylori- groups (χ(2) = 4.21, P < 0.05). A 2-year follow-up showed significant difference in the rates of metastasis and recurrence between H. pylori+/CIMP+ cases and the H. pylori+/CIMP- cases or CIMP- cases associated with H. pylori assayed in serum (P < 0.05). However, there were no significant differences in survival rates between the two groups., Conclusion: H. pylori+/CIMP+ cases are associated with higher rates of metastasis and recurrence than H. pylori+/CIMP- cases. Serum may be useful for examining CIMP status.

Objective: To investigate the association of the expressions of Th1 cytokines in gastric cancer tissue and the prognosis of patients with gastric cancer after radical resection., Methods: Fifty-eight patients with gastric cancer treated at the Zhongshan Hospital of Fudan University were retrospectively analyzed. The expressions of Th1 cytokines mRNA were detected in tumor tissues by real-time polymerase chain reaction(RT-PCR) method in Th1 cells including TRAV10, IRF1, TBX21, CD3Z, GZMB, GATA3, and IFNG. Association of Th1 cytokines mRNA expressions and prognosis was evaluated., Results: The median follow up was 42.5(1-64) months. The 1-year survival rate was 84.5% and the 3-year survival rate was 72.4%. Univariate Cox regression analysis showed that lymph node metastasis, distant metastasis, TNM staging, lymphovascular invasion, GNLY mRNA expression, and the overall expression level of the 8 types of Th1 cells were associated with the prognosis of patients with gastric cancer(all P<0.05). The 3-year survival was 86.2% in patients with increased expression of mRNA and 58.6% in those with decreased expression. The 3-year survival was 79.6% in patients with any increase in the 8 Th1 cytokines and 33.3% in those with consistent downregulation of the 8 cytokines. Multivariate Cox analysis showed that lymph node metastasis and the overall expression level of 8 Th1 cytokines were independent risk factors associated with the prognosis of patients with gastric cancer in this cohort(both P<0.05)., Conclusions: The mRNA expression of GNLY is associated with the prognosis of patients with gastric cancer but is not an independent risk factor. The combination of mRNA expressions of the eight cytokines is an independent prognostic factor.

Background: This randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer., Methods: Sixty-eight gastric PC patients were randomized into CRS alone (n = 34) or CRS + HIPEC (n = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60-90 min. The primary end point was overall survival, and the secondary end points were safety profiles., Results: Major clinicopathological characteristics were balanced between the 2 groups. The PC index was 2-36 (median 15) in the CRS + HIPEC and 3-23 (median 15) in the CRS groups (P = 0.489). The completeness of CRS score (CC 0-1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups (P = 1.000). At a median follow-up of 32 months (7.5-83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8-8.2 months) in CRS and 11.0 months (95% confidence interval 10.0-11.9 months) in the CRS + HIPEC groups (P = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events (P = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0-1, systemic chemotherapy ≥ 6 cycles, and no serious adverse events were independent predictors for better survival., Conclusions: For synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.

The N-myc downstream-regulated gene-1 (NDRG1) has recently been proposed as a metastasis suppressor, but its precise role remains unclear. To investigate whether NDRG1 can indeed influence the metastasis progress, expression of endogenous NDRG1 was knocked down in human AGS gastric adenocarcinoma cells using RNA interference. Stable NDRG1 "silenced" transfectants showed similar growth rates as their control counterparts. By contrast, invasive ability in Matrigel invasion activity and Gelatinolytic activity by matrix metalloproteinase-2 (MMP-2) were markedly increased in NDRG1 "silenced" cells. Moreover, re-expression of NDRG1 by recombinant adenovirus Ad-NDRG1 in NDRG1 "silenced" cells inhibited the increased invasive ability. Further study, we found the induction of MMP-2 by downregulation of NDRG1 was mediated by MT1-MMP. Altogether, our results imply that NDRG-1 could play a key role in the regulation of cellular invasion and metastasis, which may involve the upregulation of matrix metalloproteinases.

Objective: To investigate the incidence of pancreatic fistula following D(2) gastrectomy and associated risk factors., Methods: A total of 132 consecutive cases of gastric cancer underwent D(2) gastrectomy between Jul 1, 2009 and Dec 2009. Amylase concentration of the drainage fluid and serum amylase concentration were tested on day 1, 4, 7 after operation. Univariate analyses were performed to evaluate the significance of various covariates as risk factors for the pancreatic fistula-related complications., Results: The incidence of pancreatic fistula was 17.4%. None of the following factors including age, gender, tumor location, tumor stage, N stage, range of resection, fistula output, and serum amylase were associated with pancreatic fistula., Conclusion: The incidence of pancreatic fistula following D(2) gastrectomy is high. Drainage tube is necessary to prevent serious complications.

Background/aims: Gastric cancer (GC) is the leading cause of death in China. Although surgery based comprehensive treatment is the best approach to improve survival, postoperative recurrence is a major problem. This study was aimed to find out the relationship of cancer recurrence with major clinico-pathological factors, with special attention focused on time of recurrence., Methodology: Data of 59 recurrences after surgery among 286 GC patients were systemically collected and analyzed. Time of recurrence, the relationship between clinical stages and time of recurrence, and between number of adjuvant chemotherapy cycles and time of recurrence were evaluated., Results: 76.3% (45/59) recurrence happened within 1 year after surgery. Median time to recurrence was 7 months. Most recurrences were locoregional recurrence (57.6%). The differences in time of recurrence among stage I, stage II, stage III and stage IV were statistically not significant (p > 0.05, Kruskal-Wallis Test). There were significant differences among different adjuvant chemotherapy cycles for time to recurrence (p = 0.014, Kruskal-Wallis Test)., Conclusion: Close monitoring and active followup of patients with GC should be conducted over the first 2 years after operation. Adjuvant chemotherapy could prolong recurrence-free survival.

Objective: To evaluate the technical feasibility, effectiveness, and safety of robot-assisted gastrectomy(RAG) with lymphadenectomy using the Da Vinci system., Methods: A total of 9 patients in our institute from March 17 to April 24 2010 underwent RAG. Clinicopathologic characteristics and surgical outcomes were summarized., Results: All operations were performed successfully without conversion to either open or laparoscopic approach. There were 5 total gastrectomies,2 distal gastrectomies, 1 proximal gastrectomy and 1 wedge gastrectomy with D(1) or D(2) lymphadenectomy. The total operative time was 150 to 440 minutes. Total blood loss ranged from 10 to 100 ml. The ranges of harvested lymph nodes were 19-24 for D(1) patients and 28-38 for D(2) patients. There was 1 case of postoperative gastric leakage, which were managed conservatively., Conclusions: RAG with lymphadenectomy can be applied safely and effectively for patients with gastric cancer.

Objective: To find out a simple and reproductive prognostic index in gastric cancer patients,which can be used as a comparable parameter among different regions of China., Methods: The perigastric metastatic lymph nodes(PGMLN) with long-term survival data were retrospectively evaluated in 148 gastric cancer patients, undergone potentially curative resections., Results: The 3-year cumulative survival rate was 62.8% and the survival rate decreased significantly with the increase of PGMLN, especially when the PGMLN was more than 6. The PGMLN had a clear linear relationship with total positive lymph nodes(r=0.94, P<0.01), while it had little correlation with total resected lymph nodes(r=0.18,P=0.2)., Conclusions: PGMLN is a convenient and reliable prognostic factor in gastric cancer patients, which may be a good candidate of comparable parameters among different regions of China.

12-Lipoxygenase (12-LOX) is over-expressed in a variety of human tumors, but its exact effect on the tumorogenesis of gastric cancer remains largely obscure. To investigate the effect of 12-LOX and its inhibitor baicalein on proliferation and apoptosis of human gastric cancer, AGS cells were separately treated with 12-hydroxyeicosatetraenoic acid (12-HETE, a metabolite of 12-LOX) and baicalein. MTT assay revealed that the absorbance of the 12-HETE-treated group was significantly (P < 0.01) higher than that of control group and that the absorbance of baicalein-treated group was significantly (P < 0.01) less than that of the control group, and that 48 h after treatment the apoptosis index of the baicalein-treated group was significantly (P < 0.01) higher than that of the untreated group and was significantly (P < 0.01) lower in the 12-HETE-treated group. Western blotting analysis was used to investigate the mechanism of these effects. The results revealed that the concentration of phosphorylated ERK in cells treated with 100 nmol L(-1) 12-HETE was significantly (P < 0.05) higher than in the untreated group and that the concentration of phosphorylated ERK1/2 in cells treated with 40 micromol L(-1) baicalein was significantly (P < 0.05) lower than in the untreated group. The expression level of bcl-2 was up-regulated and down-regulated after separate treatment with 12-HETE and baicalein, respectively, and both of these effects could be blocked by PD98059. Protein kinase C (PKC) activity was increased by treatment with 12-HETE and reduced by treatment with baicalein (P < 0.05). The PKC inhibitor BIM (bisindolymaleimide-I) blocked the phosphorylation of ERK1/2 and activation of PKC induced by 12-LOX. When pretreated with BIM, the concentration of phospho-ERK1/2 or bcl-2 in the BIM + 12-HETE-treated group was significantly (P < 0.05) lower than in that treated with 12-HETE only, and the concentration in the BIM + baicalein-treated group was significantly (P < 0.05) higher than in that treated with baicalein only. On the basis of these data we conclude that, via its metabolite 12-HETE, 12-LOX abolishes proliferation of AGS cells and protect cells from apoptosis by activating the ERK1/2 pathway and, eventually, enhances expression of bcl-2. Because PKC is also involved in the activation of ERK1/2 induced by 12-LOX, 12-LOX inhibitors would be potentially powerful anticancer agents for prevention and cure of human gastric cancer.

Aim: To evaluate the potential role of Nimesulide, a selective COX-2 inhibitor, in proliferation and apoptosis of gastric adenocarcinoma cells SGC7901., Methods: Cell counts and MTT assay were used to quantify the influence of Nimesulide in the proliferation of SGC7901 cells. Transmission electron microscopy and flow cytometry were used to observe the induction of Nimesulide the apoptosis of SGC7901 cells and influence in the distribution of cell cycle. The expression of P27(kip1) protein was observed by immunocytochemical staining., Results: SGC-7901 Cells treated with Nimesulide at various concentrations exhibited a profound dose- and time-dependent reduction in the proliferation rate over the 72 h test period. The highest survival rate of the cells was 78.7 %, but the lowest being 22.7 %. Nimesulide induced apoptosis of the cells in a dose-dependent and non-linear manner and increased the proportion of cells in the G(0)/G(1) phase and decreased the proportion in the S and G(2)/M phase of the cell cycle. Meanwhile, Nimesulide could up-regulate the expression of P27(kip1) protein., Conclusion: The induction of apoptosis and cell cycle arrest are both anti-proliferative responses that likely contribute to the antineoplastic action of nimesulide on SGC-7901 cells. The up-regulation of P27(kip1) gene may contribute to the accumulation of these cells in the G(0)/G(1) phase following treatment with Nimesulide. Selective COX-2 inhibitor may be a new channel of the chemoprevention and chemotherapy for gastric carcinoma.