The Cytotoxic Effect And Mechanisms For Thermochemotherapy Of 5-fu To Human Gastric Cell Line

Gastric cancer is the most aggressive solid malignancy in china. Most patients have been advanced before being diagnosed for the reason of no striking clinical syndrome during early stage of gastric cancer development.ObjectivesThis study was to investigate the effect of chemohyperthermia on gastric cancer cells in vitro and approach the possible mechanisms .MethodsThe human gastric carcinoma SGC-7901 cell line was incubated with different concentrations of 5-FU for different temperatures, the morphology of the cells was observed under a microscope; the cell apoptosis was measured by FCM using Annexin V/PI; The gene expression profile was analysed by the Human Apoptosis Gene Array.Results1. Either simple thermotherapy or chemohyperthermia displayed considerable killing effects on cancer cells which were confirmed by microscope observation, and a great deal of dead cells were observed when treated with chemohyperthermia.2. Significant synergistic effect was observed when the gastric cancer cell lines were treated with 5-FU in combination with elevated hyperthermia from 43℃to 45℃ compared with control group ( P<0.05) . The strongest effect was achieved at 45℃.3. Judged with the Veleriote method,there was obvious synergism of 5-FU 500μg/ml combined with 40-45℃hyperthermia.4. 5 genes up-regulated, including Fas-L,Bax,Caspase 3,Caspase 9,Apaf-1, and 2 genes down-regulated, including Bcl-2,Bag-1, were found with Gene Array.Conclusions1. Chemohyperthermia reveals relatively satisfactory antitumor effects with sensitization for temperature of 40-43℃and obvious synergism for temperature of 43-45℃.2. The best temperature for Chemohyperthermia is 43℃.3. Chemohyperthermia could induce apoptosis of SGC-7901 cells via up-regulate Fas-L,Bax,Caspase 3,Caspase 9,Apaf-1 and down-regulate Bcl-2,Bag-1,which might be mediated by multiple signal transduction pathways.