阻断PI3K/Akt通路增强缺氧环境胰腺癌细胞化疗敏感性的实验研究  

An experimental investigation on strengthening the sensitivity of chemotherapy for pancreatic cancer cell in hypoxia circumstance by blocking PI3K/Akt signal transduction pathway

作　　者：谢祚启[1,2] 赵秋[2] 朱亮[2] 朱珍妮[3] 

机构地区：[1]武汉市柏泉劳教所卫生所,湖北武汉430042 [2]华中科技大学同济医学院附属同济医院消化内科 [3]华中科技大学同济医学院附属同济医院感染科

出　　处：《胃肠病学和肝病学杂志》2011年第7期675-677,共3页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的研究LY294002联合吉西他滨是否能增强缺氧环境下胰腺癌细胞株PANC-1的化疗敏感性。方法缺氧条件下培养胰腺癌细胞株PANC-1,运用MTT检测LY294002联合吉西他滨对胰腺癌细胞株细胞PANC-1生长的影响,运用Western blot检测AKT及磷酸化AKT蛋白表达的水平。结果 MTT检测在缺氧环境下LY294002联合吉西他滨作用的胰腺癌细胞PANC-1与单纯吉西他滨作用组相比细胞生存率显著下降(P=0.003),且具有时间依赖性。Western blot检测显示在缺氧环境下,LY294002联合吉西他滨作用的胰腺癌细胞PANC-1磷酸化AKT蛋白水平与单纯吉西他滨作用组相比显著降低(P=0.002)。结论阻断PI3K/Akt通路能增强缺氧环境下胰腺癌细胞化疗敏感性,为胰腺癌的治疗方法及逆转耐药提供了新的实验依据。Objective To investigate whether LY294002 combined with Gemcitabine can strengthen the sensitivity of chemotherapy for pancreatic cancer cell strain PANC-1 under hypoxic circumstance.Methods Pancreatic cancer PANC-1 cells were cultured under hypoxic circumstance.The effect of treatment with both LY294002 and Gemcitabine on the growth of PANC-1 cells in hypoxia was detected by MTT,and the protein level of AKT and phosphorylated AKT were measured by Western blot.Results MTT assay showed that the survival rate of PANC-1 cells treated with both LY294002 and Gemcitabine in hypoxia reduced more significantly than that of Gemcitabine alone group（P=0.003） in a time-dependent fashion.Otherwise,Western blot assay showed that the protein level of phosphorylated AKT in PANC-1 cells treated with both LY294002 and Gemcitabine in hypoxia decreased more significantly than that of Gemcitabine alone group（P=0.002）.Conclusion The sensitivity of chemotherapy for pancreatic cancer PANC-1 cells could be enhanced under hypoxia circumstance by blocking PI3K/Akt signal transduction pathway.Therefore,this experiment could provide a new experimental evidence for pancreatic cancer therapy and drug resistances reverse.

关 键 词：胰腺癌 吉西他滨 细胞缺氧 LY294002 PI3K/AKT通路 

分 类 号：R735.9[医药卫生—肿瘤]