| Partâ… The enhancement and mechanism of arsenic trioxide on chemosensitivity of human gallbladder cancer GBC-SD cells in vitroBackground and purpose:As one of the most lethal diseases among digestive tract tumors,lacking of specific clinical manifestations,Gallbladder cancer is usually diagnosed at advanced stages of the diseases and less can be resected.Traditional chemotherapy has not shown significant activity in gallbladder carcinoma.Arsenic trioxide(As2O3) inhibits cell growth and induces apoptosis in certain types of cancer cells including acute promyelocytic leukemia,ovarian carcinomas,and gallbladder cancer,but its effect in combineation with chemotherapy in gallbladder cancer has never been reported so far.How to enhance the effect of chemotherapy in gallbladder cancer cell lines is one of the new trends in its treatments.The aim of this study is to explore the effect and mechanism of arsenic trioxide on chemosensitivity of human gallbladder cancer cells in vitro.Methods:GBC-SD cells were cultured with different concentrations of arsenic trioxide for 24h,the proliferative activity of cells was detected by MTT methods;GBC-SD cells were treated respectively with 5-Fu(100 mg/L),adriamycin(10 mg/L),mitomycin(4 mg/L) alone or combined with arsenic trioxide respectively for 24 hours.Hoechest33258 staining was used to observe the morphologic changes of apoptosis cells and determine apoptosis;Western blot was performed to analysis the expression of Bcl-2,PARP,Caspase-3,Caspase-9 involved in apoptosis.Results:The MTT assay indicated that the growth of GBC-SD cell line could be significantly inhibited by As2O3 in a concentration dependency manner;As2O3 in gallbladder carcinoma cells could enhance the apoptosis induced by 5-Fu and adriamycin,downregulate the expression of anti-apoptotic protein Bcl-2 and upregulate the expression of apoptotic protein Caspase-3,Caspase-9 and PARP.The increase of the apoptosis was observed after the treatment of mitomycin combined with As2O3,but the expression of the protein Bcl-2,Caspase-3,Caspase-9 and PARP in cells were not changed.Conclusion:As2O3 could improve the response of GBC-SD cells to 5-Fu and adriamycin by enhancing the apoptosis of GBC-SD cells induced by them via down-regulating the expression of Bcl-2,and could improve the response of GBC-SD cells to mitomycin as well.But the mechanism behind it remains unknown. Partâ…¡Enhancement of Radiation Response by arsenic trioxide in human gallbladder cancer cells in vitroBackground and purpose:Gallbladder cancer is one of the most lethal diseases in digestive tract tumors,lacks of specific clinical manifestations,and is usually diagnosed at advanced stages of the diseases and even fewer can be resected. Traditional radiotherapy has not shown significant activity in gallbladder carcinoma. Enhancement of radiation response in gallbladder cancer cells is one of the new trends in its treatments.This study is to observe the enhancement effect of arsenic trioxide (As2O3) on response of human gallbladder cancer to ionizing radiation(IR). Methods:The clonogenic survival assays were performed with increased dose (0,2,4,6,8,10 Gy) of IR alone and in combination with the concentration of As2O3 (0.2μmol/L).Results:The pretreatment of cells with As2O3 did not significantly affect the clonogenic survival at the dose of 0.2μmol/L alone,however when IR treatment was combined with As2O3,the clonogenic survival of GBC-SD cells was synergistically reduced,Dq,Do value was decreased,and the sensitizing enhancement ratio was 1.5131.Conclusions:These results indicate that As2O3 can synergistically enhance radiosensitivity of human GBC-SD cells in vitro.
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