P13K／Akt／mdm2信号通路活化对胃癌细胞阿霉素敏感性的影响  

Impact of PI3K/Akt/mdm2 signalinoo pathway on the sensitivity of gastric cancer cell line SGC7901 to doxorubicin

作　　者：艾耀伟[1] 于红刚[1] 于皆平[1] 杨艳[1] 李欢[1] 胡晓雯[1] 罗和生[1] 

机构地区：[1]武汉大学人民医院消化内科,430060

出　　处：《中华肿瘤杂志》2008年第7期494-497,共4页Chinese Journal of Oncology

基　　金：国家自然科学基金资助项目（30300154）

摘　　要：目的 研究P13K／Akt／mdm2信号通路活化对胃癌细胞阿霉素（DOX）敏感性的影响。方法分别用DOX和P13K特异性抑制剂wortmannin处理胃癌细胞株SGC7901，采用流式细胞仪检测肿瘤细胞的凋亡，免疫沉淀法检测P13K活性，Westernblot法检测P13K-p85、phospho-Akt（S473）、phospho-mdm2（S166）、Akt和p-S3的表达。结果DOX能诱导胃癌细胞SGC7901凋亡，且凋亡率与作用时间密切相关，联合应用wortmannin后，可促进胃癌细胞凋亡。DOX作用SGC7901细胞3、6、12和24h后，P13K活性逐渐增强，分别为（8．4±1．7）％、（12．7±2．1）％、（17．4±3．2）％和（16．8±2．4）％；同时，还促进Akt、mdm2磷酸化和p53表达。wortmannin可以抑制mdm2磷酸化，进一步增强p-S3的表达。结论DOX可以诱导P13K／Akt通路异常激活，并通过促进mdm2磷酸化降低胃癌细胞化疗敏感性。Objective To explore whether PI3K/Akt/mdm2 signalling pathway affect the sensitivity of gastric cancer cell line SGC7901cells to doxorubicin. Methods Gastric cancer cell line SGC7901 cells were exposed to doxorubicin and specific PI3K inhibitor wortmannin. Cell apeptosis was detected using flow cytometry. PI3K activity was detected by radioactive immunoprecipitation-kinase assay. Western blotting was employed to evaluate the expressions of PI3K-p85, pAkt-S473, Akt, pmdm2-S166 and p53. Results The level of apeptosis in gastric cancer SGC7901 cells treated with doxorubicin was gradually increasing. wortmannin enhanced its effects significantly. PDK activity and the expression of pAkt-S473 increased in a time-dependent manner, pmdm2-S166, p53 were also increased, wortmannin inhibited phosphorylation of mdm2 and improved the p53 expression. Conclusion PDK/Akt/mdm2 signalling pathway can be activated by doxorubicin and suppress apeptosis by promoting phosphorylation of mdm2. PI3K inhibitor wortmannin can enhance sensitivity of gastric cancer cells to chemotherapy.

关 键 词：磷脂酰肌醇3-激酶 丝氨酸/苏氨酸激酶 鼠双微基因2 胃肿瘤 

分 类 号：R686[医药卫生—骨科学]