| Resveratrol and proanthocyanidin have been studied for more than 30 years. Earlier studies of resveratrol and proanthocyanidin focused on their activities against bacteria, inflammation, allergy, oxidation, and free radicals, but their anti-tumor activity had not received much attention until recently. Recent studies have demonstrated that resveratrol have significantly inhibitory effects on the growth of breast cancer, prostate cancer and others. There were only few reports about the effects of the proanthocyanidin on tumors, which showed that proanthocyanidin could inhibit the growth of breast and lung cancer cells.Although resveratrol and proanthocyanidin can inhibit the growth and induce apoptosis of many tumorells, the detailed molecular mechanisms of the two agents are not clear. Different cancer cells have different sensitivity to the two agents. The effects of the two drugs on signal transduction pathways are diverse. Certain signaling molecules are affected by the two agents. Systematic and detailed studies of the anti-tumor activities and mechanisms of the two drugs on different cancer cells will help to develop better drugs and design better strategies to treat cancer patients and to decrease cytotoxicity of the two agents.Gastric cancer has a high degree of malignancy and is easy to metastasize. There are few reports about the effects of the two agents on gastric cancer, and there is no reported study for their mechanisms. In this study, we characterized the effects of resveratrol and proanthocyandin on gastric cancer cells analyzed the effects of the two agents on several important cell signal transduction molecules related to cell proliferation and survival.Normal epithelial cells undergo apoptosis when they lose cell-matrix contact. Thisphenomenon is called anoikis. The significance of anoikis is that it may prevent accidentally detached cells from reattaching to new matrices and growing dysplastically. The cells detached from tumors however do not undergo apoptosis and can colonize elsewhere and grow. The resistance to anoikis of some malignant tumor cells is one of the important reasons for tumor to metastasize. Anoikis resistance offers a good model for studying signal transduction pathways participating in cell survival, death, and metastasis. Elucidating the signal transduction mechanisms of anoikis will offer new ideas for prevention of tumor metastasis. In this study, we investigated anoikis resistance of gastric cancer cells. We analyzed the role of several important signaling molecules in anoikis resistance of gastric cancer cells. To understand the function of two of the signaling molecules, paxillin and p130cas, in anoikis resistance, we applied the RNA interference technology to silence their genes.The major findings of present study are:l.Resveratrol and proanthocyanidin have time-dependent and dose-dependent inhibitory effect on the growth of gastric cancer cells and could induce apoptosis and anoikis of the gastric cancer cells (BGC823, SGC790K HGC27, MGC803). The effects of the proanthocyanidin are stronger than that of resveratrol. These data suggest that proanthocyanidn may have advantages over resveratrol in the gastric cancer therapy.2.Different doses of resveratrol and proanthocyanidin and different culture time had different effects on gastric cells in different culture conditions ( cultured as attached versus in suspension).3.The molecular mechanism of resveratrol and proanthocyanidin-induced gastric cancer cell apoptosis(1)Resveratrol and proanthocyanidin could induce gastric cancer cells apoptosis by inhibiting the activities of certain important protein tyrosine kinases. Proanthocyanidin could also inhibit the activities of certain phosphatases inside the cells and cause imbalance in cell signaling molecules, which leads to inhibition of cell growth and induction of apoptosis.(2)The decreased activities of ERK and FAK, and increased activity of Pyk2 may participate in the induction of apoptosis of gastric cells by resveratrol and proanthoc...
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