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Colorectal cancer (CRC) is one of the leading causes of cancer‑associated mortality. Asiaticoside (AC) exhibits antitumor effects; however, to the best of our knowledge, the biological function of AC in CRC cells remains unclear. Therefore, the aim of the present study was to investigate the effect of AC on CRC cells. In the present study, CCK‑8 and colony formation assays were performed to assess the effects of AV on human CRC cell lines (HCT116, SW480 and LoVo). Mitochondrial membrane potential was examined by JC‑1 staining. Cell apoptosis and cell cycle were monitored by flow cytometry, and the expression of genes was evaluated using RT‑qPCR and western blot analysis. Furthermore, the biological effect of AC in vivo was detected using a xenograft mouse model. The findings revealed that 2 µM AC suppressed the proliferation of CRC cells in a time‑ and dose‑dependent manner, but had no adverse effects on normal human intestinal FHC cells at a range of concentrations. AC decreased the mitochondrial membrane potential and increased the apoptosis of CRC cells in a dose‑dependent manner. Furthermore, AC induced cell cycle arrest at the G0/G1 phase. AC attenuated IκBα phosphorylation in a dose‑dependent manner, thereby preventing P65 from entering the nucleus, and resulting in inhibition of the NF‑κB signaling pathway. In addition, AC significantly reduced the expression of CDK4 and Cyclin D1 in a dose‑dependent manner, significantly upregulated the activation of caspase‑9 and caspase‑3, and decreased the Bcl‑2/Bax mRNA ratio. Furthermore, treatment with the NF‑κB signaling pathway inhibitor JSH‑23 significantly increased the cytotoxicity of AC in CRC cells. Findings of the xenograft mice model experiments revealed that AC significantly inhibited colorectal tumor growth in a dose‑dependent manner. Overall, AC suppressed activation of the NF‑κB signaling pathway by downregulating IκBα phosphorylation. This resulted in inhibition of CRC cell viability and an increase of cell apoptosis, which may form the basis of AC use in the treatment of patients with CRC.

Tamoxifen is the gold standard for breast cancer endocrinotherapy. However, drug resistance remains a major limiting factor of tamoxifen treatment. Long non‑coding (lnc) RNA serves an important role in drug resistance; however, the molecular mechanisms of tamoxifen resistance in breast cancer endocrinotherapy are largely unclear. lncRNA urothelial cancer associated 1 (lncRNA UCA1, UCA1) has been proven to be dysregulated in human breast cancer and promotes cancer progression. In the present study, it was demonstrated that UCA1 was significantly upregulated in breast cancer tissues compared with healthy tissues. Furthermore, the expression level of UCA1 was significantly greater in tamoxifen‑resistant breast cancer cells (LCC2 and LCC9) when compared with those in the tamoxifen‑sensitive breast cancer cells (MCF‑7 and T47D). UCA1 silencing in LLC2 and LLC9 cells increased tamoxifen drug sensitivity by promoting cell apoptosis and arresting the cell cycle at the G2/M phase. Notably, the induced overexpression of UCA1 in MCF‑7 and T47D cells decreased the drug sensitivity of tamoxifen. The molecular mechanism involved in UCA1‑induced tamoxifen‑resistance was also investigated. It was identified that UCA1 was physically associated with the enhancer of zeste homolog 2 (EZH2), which suppressed the expression of p21 through histone methylation (H3K27me3) on the p21 promoter. In addition, it was demonstrated that UCA1 expression was paralleled to the phosphorylation of CAMP responsive element binding protein (CREB) and AKT. When LCC2 cells were treated with the phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway inhibitor LY294002, the phosphorylation levels of CREB and AKT were significantly downregulated. Taken together, it was concluded that UCA1 regulates the EZH2/p21 axis and the PI3K/AKT signaling pathway in breast cancer, and may be a potential therapeutic target for solving tamoxifen resistance.

The effect of hyperthermic carbon dioxide (CO2) pneumoperitoneum in combination with 5-fluorouracil (5-FU) on the proliferation and invasion of colon cancer was explored. Colon cancer cell line SW-480 was sealed into the urine collection bag to simulate pneumoperitoneum with 100% CO2 under a pressure of 12 mmHg. The cells were divided into group A, CO2 at 37˚C; group B, CO2 at 43˚C; group C, 5-FU; group D, CO2 at 37˚C+5-FU; group E, CO2 at 43˚C+5-FU; and control groups under normal culture conditions. The cell proliferation was assessed by CCK-8 test; the cell apoptosis was tested by FACS analysis; the cell invasion was examined by Transwell assay; the expression of HSP-70, caspase-3, HIF-1α and MMP-9 proteins and genes were detected by western blot analysis and RT-PCR. The SW-480 cells were injected into nude mouse cecum subserosal to establish a colon cancer model. We applied 43˚C CO2 pneumoperitoneum or 5-FU intraperitoneal chemotherapy to intervene, detected the transplantation tumor growth and metastasis. The cell proliferation was inhibited in groups B, C, D and E, apoptosis was induced in groups B, C, D and E, the Transwell cell number decreased in groups B, C, D and E, the transplantation tumor weight and metastasis rate were inhibited in groups B, C, D and E, but all not in group A. The most significant change was observed in group E. Hyperthermic CO2 pneumoperitoneum was able to reinforce the inhibition of 5-FU on proliferation and invasion of colon cancer.

The present study explored the inhibitory effect of hyperthermic CO2 pneumoperitoneum on the proliferation and migration of colon cancer cells, and its mechanism. Colon cancer cell line SW-480 was sealed into a urine collection bag to simulate pneumoperitoneum with 100% CO2 under a pressure of 14 mmHg. The growth and morphology of cells were observed under a microscope, the inhibition on cell proliferation was measured using WST-8 test, cell apoptosis and the cell cycle were monitored using fluorescence-activated cell sorting analysis, the migration of cells was tested using the scratch assay, and the expression of HSP-70, caspase-3, hypoxia-inducible factor-1α (HIF-1α) and matrix metalloproteinase-9 (MMP-9) proteins and genes was investigated using western blotting and reverse transcription polymerase chain reaction. Compared with the control group, there was no significant difference in the CO2 group (P>0.05), while the apoptosis and necrosis rates in the hyperthermo-CO2 group was significantly increased (P<0.05). Compared with the control group, the number of cells at G0/G1 phase significantly increased and the number of cells at S phase significantly decreased in the hyperthermo-CO2 group (P<0.05), indicating that hyperthermo-CO2 could arrest the cell cycle. It was suggested by the results of the scratch assay that cell migration ability enhanced in the CO2 group, but decreased in the hyperthermo-CO2 group compared with the control. CO2 pneumoperitoneum promoted cell migration by upregulating HIF-1α and MMP-9 expression. However, the CO2 pneumoperitoneum with hyperthermia enhanced apoptosis and inhibited migration by upregulating the expression of HSP-70, HIF-1α and caspase-3, but downregulating the expression of MMP-9.

The class of Omega glutathione transferases is newly identified with novel structural and functional characteristics. Human GSTO 1-1 (glutathione S-transferase Omega 1) is the first member of the GST Omega class. It was found to play a role in apoptosis and be in association with age-at-onset of AD and PD. In order to improve the understanding of the properties of other Omega class members, we screened a human fetal brain cDNA library and obtained the human GSTO2 (glutathione S-transferase Omega 2) cDNA. The full-length cDNA of human GSTO2 is 1179 bp long and encodes a protein of 243 amino acid residues. Expression pattern analysis revealed that GSTO2 was ubiquitously expressed at a low level, with a higher expression in pancreas and prostate. Enzyme assays showed that GSTO2 protein had activities similar to Omega class GSTs. It has detectable glutathione-dependent thiol transferase activity and glutathione-dependent dehydroascorbate reductase activity. But different from GSTO1-1, GSTO2 exhibits a high catalytic activity with CDNB. Subcellular localization analysis of GSTO2-EGFP fusion protein revealed that GSTO2 distributed to cytoplasm of COS-7 cells and both cytoplasm and nucleus of L-02, QGY-7703 and SMMC-7721 cells. Overexpression of GSTO2 induced apoptosis of L-02 cells detected by Annexin V-PE staining. The results suggest that GSTO2 may play an important role in cellular signaling.