摘要
目的探讨阿司匹林是否引起胰腺癌细胞株SW1990对吉西他滨耐药及其可能机制。方法通过四氮唑蓝(MTT)和HOCHEST33258染色方法检测药物对人胰腺癌耐药株SW1990细胞的生长情况以及凋亡的影响;并应用蛋白免疫印迹方法检测细胞信号通路PI3K/AKT的变化。结果阿司匹林能明显降低吉西他滨对细胞的抑制率并提高IC50。0.4μmol/L吉西他滨干预细胞后,凋亡率达56%,明显高于吉西他滨与阿司匹林合用时细胞的凋亡率(28%,P<0.01)。磷酸化AKT和PI3K水平明显增高。PI3K/AKT信号通路抑制剂LY294002能明显逆转阿司匹林引起的SW1990细胞耐受吉西他滨的现象。结论阿司匹林通过激活PI3K/AKT信号通路引起胰腺癌细胞株SW1990对吉西他滨耐药。
Objective To investigate whether aspirin induces resistance to gemcitabine in human pancreatic cancer cell SW1990 and its possible mechanism.Methods Human pancreatic cancer cell SW1990 was used as an in vitro model.MTT and HOCHEST33258 staining were carried on to evaluate cell growth and apoptosis.Wester blot was taken to access the effects of aspirin on the PI3K/AKT signaling pathway.Results The viability of human pancreatic cancer cell SW1990 was inhibited to 50% compared to control,after treatment with 0.4 μmol/L gemcitabine for 72 h.The IC50 for gemcitabine in SW1990 cells was（0.42±0.05）μmo/L.Aspirin was able to significantly block the inhibitory effect of gemcitabine on cell viability and increase the IC50 for gemcitabine.Gemcitabine at the dose of 0.4 μmol/L was enough to trigger 56% apoptosis in cancer cells,which was higher than the combination of aspirin and gemcitabine.The level of phosphorylated protein of AKT and PI3K were profoundly raised by aspirin.Furthermore,the inhibitor of PI3K/AKT,LY294002,could reverse the interference of aspirin.Conclusion Aspirin is able to induce resistance to gemcitabine in human pancreatic cancer cell SW1990 though activation of PI3K/AKT signaling pathway.
出处
《重庆医学》
CAS
CSCD
北大核心
2010年第17期2267-2269,F0002,共4页
Chongqing medicine
关键词
胰腺癌
阿司匹林
吉西他滨
human pancreatic cancer
aspirin
gemcitabine
