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Chalcone is a common scaffold found in many biologically active compounds. The chalcone scaffold was also frequently utilized to design novel anticancer agents with potent biological efficacy. Aiming to continue the research of effective chalcone derivatives to treat cancers with potent anticancer activity, fourteen amino chalcone derivatives were designed and synthesized. The antiproliferative activity of amino chalcone derivatives was studied in vitro and 5-Fu as a control group. Some of the compounds showed moderate to good activity against three human cancer cells (MGC-803, HCT-116 and MCF-7 cells) and compound 13e displayed the best antiproliferative activity against MGC-803 cells, HCT-116 cells and MCF-7 cells with IC50 values of 1.52 &mu, M (MGC-803), 1.83 &mu, M (HCT-116) and 2.54 &mu, M (MCF-7), respectively which was more potent than the positive control (5-Fu). Further mechanism studies were explored. The results of cell colony formatting assay suggested compound 10e inhibited the colony formation of MGC-803 cells. DAPI fluorescent staining and flow cytometry assay showed compound 13e induced MGC-803 cells apoptosis. Western blotting experiment indicated compound 13e induced cell apoptosis via the extrinsic/intrinsic apoptosis pathway in MGC-803 cells. Therefore, compound 13e might be a valuable lead compound as antiproliferative agents and amino chalcone derivatives worth further effort to improve amino chalcone derivatives&rsquo, potency.

The Hippo pathway is widely considered to inhibit cell growth and play an important role in regulating the size of organs. However, recent studies have shown that abnormal regulation of the Hippo pathway can also affect tumor invasion and metastasis. Therefore, finding out how the Hippo pathway promotes tumor development by regulating the expression of target genes provides new ideas for future research on targeted drugs that inhibit tumor progression. PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched. The search strategy identified 1892 hits and 196 publications were finally included in this review. As the core molecule of the Hippo pathway, YAP/TAZ are usually highly expressed in tumors that undergo invasion and migration and are accompanied by abnormally strong nuclear metastasis. Through its interaction with nuclear transcription factors TEADs, it directly or indirectly regulates and the expressions of target genes related to tumor metastasis and invasion. These target genes can induce the formation of invasive pseudopodia in tumor cells, reduce intercellular adhesion, degrade extracellular matrix (ECM), and cause epithelial-mesenchymal transition (EMT), or indirectly promote through other signaling pathways, such as mitogen-activated protein kinases (MAPK), TGF/Smad, etc, which facilitate the invasion and metastasis of tumors. This article mainly introduces the research progress of YAP/TAZ which are the core molecules of the Hippo pathway regulating related target genes to promote tumor invasion and metastasis. Focus on the target genes that affect tumor invasion and metastasis, providing the possibility for the selection of clinical drug treatment targets, to provide some help for a more in-depth study of tumor invasion and migration mechanism and the development of clinical drugs.

Piperlongumine (PL) is a very promising natural agent with a high potential for cancer treatment. To overcome the poor water solubility of PL, there is a need to develop a novel water-soluble formulation in which PL is non-covalently bound to human serum albumin (HSA). PL binding to HSA was studied by various spectroscopic techniques under simulated physiological conditions. Spectroscopic evidence showed that the interaction of PL with HSA could form a PL-HSA complex. The binding constant (Ka ) values increased with increasing temperature, and a similar dependence was observed for the number of binding sites (n) values. The number of PL molecules bound to HSA reached 8.1 when the temperature was raised to 308 K. Thermodynamic calculation results suggested that the binding reaction occurred spontaneously but was an entropy-driven process, and hydrophobic forces played a major role in stabilizing the complex. Furthermore, PL binding induced conformational and microenvironmental changes in HSA. Displacement studies indicated that PL and warfarin had separate binding regions in site I. Therefore, it would be possible to develop a novel water-soluble formulation involving PL and HSA. This study may provide some valuable information in terms of improving the poor water solubility of PL.

Pancreatic cancer is a polygenic disease and the fourth leading cause of cancer-associated mortality worldwide; however, the tumorigenesis of pancreatic cancer remains poorly understood. Research at a molecular level, which includes the exploration of biomarkers for early diagnosis and specific targets for therapy, may effectively aid in the diagnosis of pancreatic cancer in its early stages and in the development of targeted molecular-biological approaches for treatment, thus improving prognosis. By conducting expression profiling in para-carcinoma, carcinoma and relapse of human pancreatic tissues, 319 genes or transcripts with differential expression levels >3-fold between these tissue types were identified. Further analysis with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes demonstrated that the translation, nucleus assembly processes and molecular functions associated with vitamin B6 and pyridoxal phosphate binding in pancreatic carcinoma were abnormal. Pancreatic cancer was additionally identified to be closely associated with certain autoimmune diseases, including type I diabetes mellitus and systemic lupus erythematosus.

The interactions between human serum albumin (HSA) and fluphenazine (FPZ) in the presence or absence of rutin or quercetin were studied by fluorescence, absorption and circular dichroism (CD) spectroscopy and molecular modeling. The results showed that the fluorescence quenching mechanism was static quenching by the formation of an HSA-FPZ complex. Entropy change (ΔS0 ) and enthalpy change (ΔH0 ) values were 68.42 J/(mol⋅K) and -4.637 kJ/mol, respectively, which indicated that hydrophobic interactions and hydrogen bonds played major roles in the acting forces. The interaction process was spontaneous because the Gibbs free energy change (ΔG0 ) values were negative. The results of competitive experiments demonstrated that FPZ was mainly located within HSA site I (sub-domain IIA). Molecular docking results were in agreement with the experimental conclusions of the thermodynamic parameters and competition experiments. Competitive binding to HSA between flavonoids and FPZ decreased the association constants and increased the binding distances of FPZ binding to HSA. The results of absorption, synchronous fluorescence, three-dimensional fluorescence, and CD spectra showed that the binding of FPZ to HSA caused conformational changes in HSA and simultaneous effects of FPZ and flavonoids induced further HSA conformational changes.

The aim of this study was to investigate the antitumor effect of a plasmid co-expressing ENDO-VEGI151 and survivin siRNA on breast cancer in nude mice, and to explore the feasibility of attenuated Salmonella typhimurium (S. typhimurium) as a delivery vector for cancer gene therapy in vivo. Three recombinant expression plasmids pENDO‑VEGI151 (pEV), pSurvivin-siRNA (psi-survivin) and co-expressing plasmid pENDO-VEGI151/survivin‑siRNA (pEV/si-survivin), were transferred into the attenuated S. typhimurium strain SL7207, respectively. MDA-MB-231 cells were infected with these recombinants in vitro, and the expression of ENDO-VEGI151 and survivin was detected. In order to detect S. typhimurium distribution and gene delivery efficiency in vivo, the plasmid pEGFP-N1 which encodes green fluorescent protein was transferred into SL7207, and the recombinant known as SL-pEGFP was orally administered to tumor-bearing nude mice. The gene transfer efficiency, distribution and survival time of the SL-pEGFP in vivo were evaluated by detection of GFP fluorescence. SL-pEGFP not only infected the cancer cells effectively, but also allowed the survival and expression of specific genes mainly in the xenografts of nude mice. To further identify the anticancer effects of these recombinants in vivo, mice burdened with xenografts were randomly divided into 6 groups, which were subjected to intragastric administration of vehicle, SL7207, SL-pcDNA3.1, SL-pEV, SL-psi-survivin and SL-pEV/si-survivin, respectively. Eight weeks after implantation, tumor size, weight, inhibition rate, intratumoral microvessel density (MVD), apoptotic index (AI), ENDO‑VEGI151 and survivin expression were evaluated. Compared with the SL-pEV or SL-psi-survivin-treated groups, the growth of tumors was significantly reduced in the SL-pEV/si-survivin group with an inhibition rate of 90.28 vs. 69.12 and 65.61%, respectively. MVD and the expression of survivin were decreased significantly in the SL-pEV/si-survivin-treated group, while AI increased significantly in the SL-pEV/si-survivin-treated group. These results indicated that attenuated S. typhimurium carrying the dual function plasmid pEV/si-survivin cannot only be specifically enriched in the tumor tissue, but also showed a synergistic antitumor effect in vivo.

Background: Prostate carcinoma is a major cause of morbidity and mortality. The MAPK Signaling Pathway plays an important role in multiple tumors, including prostate carcinoma. MAPK signaling is mediated by ERK1/2, JNK and p38 MAPK, which are important in the control of cell proliferation, differentiation and apoptosis. However, relatively little is known about the regulatory mechanism of p38 MAPK in prostate cancers. NOB1 is among the most novel topic in MAPK studies currently. Recent studies found its vital role in tumor metastasis in glioblastoma proliferation, however, its expression profile and its prognostic value in prostate carcinoma have not been investigated. Methods: To determine the relationship between NOB1 and p38 MAPK expressions, a population-based study was conducted for immunohistochemical staining analysis of tumor tissues, in matched malignant and nonmalignant prostatectomy samples from 132 PCa patients. Moreover, Western blot analysis and NOB1 interference studies of prostate cancer cell lines. To evaluate the diagnostic and prognostic between NOB1 and p38 MAPK in prostate cancer (PCa) tissue after radical prostatectomy, the hypothesis that prostate cancers with NOB1 expression have distinct clinical, prognostic and molecular attributes was tested. Results: Among 132 prostate cancers, NOB1 expression was detected in 117 (88.7%) tumors by immunohistochemistry. NOB1 and p38 MAPK expression had significant positive correlation with carcinogenesis, tumor progression and patient survival. Immunohistochemically, NOB1 expression in prostate cancer was independently associated with p38 MAPK activation (P=0.0002). Furthermore, p38 MAPK expression was completely suppressed by NOB1 interference in the prostate cancer cell lines DU-145 and PC-3. Conclusions: NOB1 expression status was closely correlated with important histopathologic characteristics and the recurrence and metastasis of prostate carcinomas. These data support a potential link between NOB1 and p38 MAPK, and suggest that NOB1 may identify a subset of prostate cancer patients with a poor prognosis. This study proved that NOB1 in PCa tissue can be used, in combination with traditional clinicopathological factors, as promising diagnostic and prognostic tools.

To investigate the role of the improved MTT assay in prediction of intrinsic drug resistance of liver cancer.The convenient MTT colorimetry was innovated to test the effects of 4'-epi-adriamycin (E-ADM), carboplatin (CBP), and 5-Fluorouracil(5-Fu), used alone or in combination, on 30 specimens of primary liver cancer without chemotherapy. All of the 30 paraffin-embedded tissues were assembled in a microarray. The used terminal concentrations of drugs were one twentieth those of the plasma peak concentrations calculated by using the liver cancer cells of the line SMMC-7721. The expression of P-glycoprotein (P-gp), multidrug resistant protein (MRP)-3, lung resistance-related protein (LRP), glutathione S-transferase (GST)-pi, and 2 kinds of cyclin-related protein: p16(INK4a) and p21WAF1, were detected by immunohistochemistry.Sixteen of the 30 specimens (53.3%) were drug-resistant and 14 of the 30 specimens (46.7%) were drug-sensitive. The sequence of drug -sensitivity was in the order of combination chemotherapy, E-ADM, 5-Fu, and CBP. The positive rate of P-gp in the drug-resistant group was 56.3%, significantly higher than that of the drug-sensitive group (14.3%, P0.05).An improved MTT assay has been developed that is more scientific and worth spreading clinically. Intrinsic drug resistance of liver cancer is popular. P-gp is a good predictive marker in intrinsic drug resistance of liver cancer.

To study the effect of dexamethasone (Dex) on the apoptosis and NF-kappaB activation in Raji cells as well as expression of MMP9 and VEGF induced by As2O3, and to observe the effect of inhibited activity of NF-kappaB by Dex on apoptosis.Cell apoptosis was analysed by Annexin V. Fluctuation of NF-kappaB, MMP9 and VEGF was detected by semi-quantitative immunohistochemistry.The apoptosis and activation of NF-kappaB of Raji cells could be induced by As2O3. The percentage of apoptosis was (39.2 +/- 1.3)%. Dex significantly increased (77.5%) the apoptosis induced by As2O3 (P0.05). Dex suppressed the activation of NF-kappaB induced by As2O3 (a suppression rate of 28.0%, P0.05). There was a positive correlation between the changes of MMP9, VEGF and NF-kappaB.As2O3 could induce apoptosis, activate NF-kappaB and up-regulate expression of MMP9 and VEGF of Raji cells. The mechanism of enhanced apoptosis by Dex may be related to suppressing activation of NF-kappaB and down-regulating expression of MMP9 and VEGF.