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Abstract: Patients with advanced hepatocellular carcinoma (HCC) have shown to benefit from tamoxifen treatment. The mechanisms of tamoxifen effects in HCC, however, are not yet clearly understood. The PI3K/Akt/mTOR signal pathway is involved in cell proliferation, tumorigenesis, and apoptosis. Over-expression of survivin has played an important role in leading to antiapoptosis. The current study investigated changes in mTOR pathway and survivin expression in hepatocarcinoma cell line HepG2 treated with tamoxifen. We detected apoptosis of hepatocarcinoma cells by flow cytometry assay. Survivin transcription level and p70S6k was demonstrated by PCR, dual-luciferase reporter assay and western blot analysis respectively. Our results are showed as follows: tamoxifen leads to apoptosis of the cells, and reduction in survivin expression, as well as a dramatic reduction in the activated form of p70S6 kinase. Twenty micromoles tamoxifen treatment signifcantly depresses transcription of survivin mRNA. Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduce survivin protein level but did not affect survivin transcription, which indicated that tamoxifen and rapamycin were synergistic in regards to down-regulation of survivin expression in hepatocellular carcinoma cells. Our results suggest that tamoxifen down-regulate survivin expression in HepG2 cells is mediated by transcriptional and posttranscriptional level via PI3K/Akt/mTOR pathway to induce apoptosis. [Copyright &y& Elsevier]

Abstract: Objective: We sought to determine whether paeoniflorin enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells, and, if so, to determine the relationship between this apoptosis and NF-κB activation. Methods: Paeoniflorin was diluted to different concentrations and added to gastric carcinoma cells (SGC-7901) at different times. Western blot was used to test the expression of NF-κB in nuclear and IκBα, p-IκBα, IKKα in cytoplasm. Further, the intranuclear expression of NF-κB was confirmed by ELISA assay. The impact of paeoniflorin and 5-fluorouracil on cell apoptosis of gastric carcinoma cells was estimated by flow cytometry. Results: Paeoniflorin revealed dramatic inhibition of NF-κB activity in the nuclei of the cells. The inhibition pattern of NF-κB was exhibited in a time- and dose-dependent manner, which was confirmed by Western blot and ELISA. Decreased nuclear translocation of NF-κB induced by paeoniflorin was found by preventing IκBα phosphorylation. Moreover, 5-fluorouracil-induced cell apoptosis was promoted by paeoniflorin in gastric carcinoma cells. Conclusions: Paeoniflorin can inhibit NF-κB activity of SGC-7901 cells, and enhance 5-fluorouracil-induced apoptosis of gastric carcinoma cells. [Copyright &y& Elsevier]