The Effects Of Combination Of HCTB006and5-Fluorouracil On Human Gastric Cancer Cells MKN28、7901、BGC823

Gastric cancer is one of the common maligant tumors worldwid new cases accounted for17%of total new cancer cases per year in the world. Most patients have been found in the advanced stage and chemotherapy is the primay treatment means for them. DR5monoclonal antibodies can specificlly effect on tumor cells surface of death receptor5, which induces the apoptosis of cancer cells with no obvious toxic effect to normal cells. It would be widely applicatied in the future. We used anti-human DR5monoclonal antibody HCTB006and5-Fluorouracil acted on human gastric cancer cells in vitro, then investigate the action effects and potential mechanism of the combintion. In this study, we hope to provide new ideas for the treatment of gastric cancer.The durgs had been devided into four groups,5-FU group, HCTB006group, the combiation group, control group, respectively.12hour later, the cells morphology was observed under the microscope. The ability of HCTB006alone,5-FU alone and the combation to inhibition gastric cell proliferation was measured by ATP-lite assay12or24hours later. The expression of DR5on the surface of gastric cancer cells was examined by flow cytometry; The level of X-linked inhibitors of apoptosis (XIAP) and caspase3was detected by western blot in treated cells.After12hours of durg effection, by microscope we could see that gastric cancer cells of blank group growed tightly; cells of5-FU and HCTB006group with low density and became rounaed and wrinkled. The combation group cells were significantly reduced and the apoptosis rates increased. According to the experimental data, we could concluded that gastric cancer cells7901and MKN28is less sentivity to HCTB006. But it has time and concentration-dependent effected to BGC823cells. Concentration and time-dependent cytotoxicity of5-FU was exhibitied in7901^BGC823. MKN28cells. The combination of5-FU and HTCB006had syngergistic effect to gastrie cancer cells and the inhibition rate had no relation with drugs order. The expersssion of DR5on the surface of the gastric cancer cells7901, MKN28, BGC823is93.8%,87.7%and94.2%resprectively. Westren blot revealed that combation agents can induced X-linked inhibitors of apoptosis (XIAP) degradation and final activates caspase3, apoptosis execution protein, cleaved.The results showed that:Gastric cancer cells has different sensitivity to HCTB006. The combination of5-FU and HTCB006exhibited syngergistic effect on gastric cell with concentration-dependent. The sentivity to HCTB006of gastric cancer cell in vitro has no direct association with DR5expression; The mechanism underlying this sensitization is possible with the cleavage of apoptosis inhibitor XIAP.