The Study On Mechanisms Of Resveratrol Inducing SGC-7901 Cell Apoptosis And The Application On SGC-7901 Cell

Background and objective: Resveratrol (Res) is a naturally phytoalexin polyphenolic compound found in various plants and has been shown to exhibit a wide range of pharmacological properties and is believed to play a role in the chemoprevention and treatment of human cancer, including leukemia, lung cancer, colon cancer and breast cancer ,et al. So it is prospected to be a newly valuable pharmaceutical product to prevent and treat human cancers. Resveratrol induces apoptosis in various malignant cells through multiple mechanisms, such as up-regulation of Fas/FasL expression, enhancement of P53 expression and activity, alteration of expression of Bcl-2 family of proteins and activation of caspase. Despite of these finding, however, the effect of resveratrol on gastric cancer is still not well understood. In order to know the value of resveratrol on treatment of gastric cancer, we examinated the effects of resveratrol on the grows and apoptosis of the gastric cancer lines SGC-7901, proposed to investigate the potential mechanisms of resveratrol inducing SGC-7901 cell apoptosis, and comprehensive experimental and theoretical foundation in cure gastric cancer.Methods: (1) Processing SGC-7901 cell with a serial concentration of Res, the inhibition of cell proliferation was examined by methyhhiazdyl tetrazolium (MTT) method. TUNEL method and flow cytometry using PI staining analysis were selected to detect apoptosis. Expression of Bcl-2, Bax, Casepase-3 and Fas protein in gastric cancer cells were measured by immunohistochemistry, RT-PCR were used to detect the transcriptions of Bcl-2, Bax, Casepase-3 and Fas mRNA. (2) MTT assay was performed to detect the suppressing effect of resveratrol and AS2O3, 5- FU alone or in combination on SGC-7901 cells for 24h,48h and 72h. Middle dosage and combination index were calculated at different periods to estimate synergistic effect of resveratrol and AS2O3, 5- FU on SGC-7901 cells. After SGC-7901 cells were treated by resveratrol and AS2O3, 5- FU alone or in combnation for 48h, TUNEL method and flow cytometry (FCM) was performed to observe cell apoptosis. (3) Resveratrol in combination with plasmid of TRAIL was transfected into the SGC-7901 cells simultaneously to investigate the inhibitory effect for the tumor.Results: (1) Compared with a control, Res couldn't only up-regulated gene transcription and protein expression of Bax, Casepase-3 and Fas, but also down-regulated gene transcription and protein expression of Bcl-2. Along with Res concentration increase and action time prolongation, the inhibition rate of the proliferation of SGC7901 cells was higher than that of the control by MTT, the apoptosis rate was also higher by the flow cytometry and Karyopycnosis, nuclear chromosomal condensation and segmentation were observed by TUNEL. (2) Resveratrol could significantly induce the apoptosis of tumor with the combination of AS2O3 and 5- FU.(3) Resveratrol could significantly induce the apoptosis of tumor with the combination of plasmid of TRAIL.Conclusion: Res could inhibit the proliferation and induce apoptosis of SGC7901 cells in concentration and time dependent manners ranging from 10 to 400μmol/ L (P<0.01), these are potentially concerned with up-regulated expression of Bax, Casepase-3 and Fas, down-regulated expression of Bcl-2. The apoptosis of tumor cells were greatly increased after treatment of resvreatrol combined with AS2O3, 5- FU and plasmid of TRAIL.