【摘要】 目的探讨阿霉素诱导胃癌细胞磷脂酰肌醇3’-激酶(P I3’K)/A k t/FKHRL 1通路的激活对胃癌细胞SGC-7901化疗效果的影响及二者的关系。方法阿霉素及P I3’K/A k t抑制剂W ortm ann in分别作用于胃癌细胞SGC-7901,M TT比色法检测胃癌细胞的生存率,W estern印迹法检测FKHRL 1磷酸化表达水平。结果阿霉素抑制胃癌细胞SGC-7901的生长,呈时间依赖性诱导FKHRL 1磷酸化。W ortm ann in可明显增强阿霉素的细胞生长抑制作用,同时下调阿霉素诱导的磷酸化FKHRL 1表达。结论阿霉素可能通过激活SGC-7901细胞的P I3’K/A k t通路诱导FKHRL 1磷酸化,从而影响胃癌细胞的化疗耐药性。W ortm ann in可以阻断P I3’K/A k t/FKHRL 1通路而提高胃癌的化疗敏感性。更多还原

【Abstract】 Objective: To investigate the correlation between phosphatidylinositol-3 kinase(PI3’ K)/Akt/FKHRL1 signaling pathway and chemoresistance in human gastric cancer cell line SGC7901.Methods: Cells were exposed to Doxorubicin with or without Wortmannin(a special inhibitor of PI3’K/Akt pathway).The cytotoxicity was assessed by determining cell survival with MTT.The phosphorylation levels of FKHRL1 was evaluated in SGC-7901 cell By Western blot analysis.Results: The Doxorubicin caused reduction of cell viability of SGC-7901 and induced phosphorylation of FKHRL1 in a time-dependent manner.Wortmannin enhanced the cell inhibitory efficiency of Doxorubicin.Phosphorylation levels of FKHRL1 was significantly induced by Doxorubicin in a time-dependent manner and was blocked by Wortmannin.Conclusions: Doxorubin may activated PI3’K/Akt signaling pathway and then induced phosphorylation of FKHRL1 which decrease the chemotherapy sensitivity of gastric cancer cell SGC-7901.However,Wortmannin enhance the chemotherapy sensitivity by suppressing this pathway.更多还原