| Gastric cancer is one of the most common digesting system malignant tumor. It is reported that more than800000new gastric cancer cases happen every year in the world. Even if the early gastric cancer surgery was carried out, the tumor tend to appear recurrence and metastasis. Now the chemotherapy reimen of gastric cancer is not satisfieded in clinical, we need to find the more secure and effective chemotherapy reimen. Recently the study of DR5is become the hot spot, when it is combined with TRAIL (tumor necrosis factor-related apoptosis-inducing ligand), it can reduce the tumor cell apoptosis. XIAP (X-chromosome-linked inhibitory of apoptosis protein), one of the IAPs(inhibitors of apoptosis), for the past few years, it was said that knocking out the tumor cell XIAP can increase the TRAIL sensitivity. In this study, we want to explore the cytotoxic effect of combined hCTB006and Irinotecan on human gastric cancer BGC823and SGC7901cells in vitro.There are four groups in this experiment:control group, hCTB006group, Irinotecan group and the combination group. First, the expression of DR5on BGC823, SGC7901was detected by FCM (flow cytometry). Second, after the gastric cells adhere to the dish24h, added in different drugs, the cytotoxic effect of hCTB006and irinotecan, alone or in combination, was evaluated using by ATP lite assay after48h. And then, DR5expression in tumor cells was examined by using ELISA. Finally, the level of cytoplasmic XIAP was detected by Western blot.The expersssion of DR5on the surface of the gastric cancer cells SGC7901, BGC823is93.8%,94.2%resprectively. The ATPlite results showed that:Irinotecan exerted a cytotoxic effect on gastric cancer cells in a concentration-dependent manner, while the effect of hCTB006on gastric cancer cells was not concent Ration-depen-dent. hCTB006combined with Irinotecan resulted in a synergistic cytotoxic effect on BGC823cells, but not on SGC7901cells. Irinotecan treatment did not significantly alter DR5expression. Combined irinotecan and hCTB006down-regulated XIAP expression in BGC823cells, but not in SGC7901cells.Conclusion:Irinotecan can inhibit the growth of gastric cancer dose-dependently. Antihuman DR5monoclonal antibody hCTB006and irinotecan exert a synergistic cytotoxic effect on gastric cancer cells possibly by regulating the expression of XIAP. |
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