17-AAG通过抑制Erk信号通路增强奥沙利铂诱导结肠癌细胞凋亡  

17-Allylamino-17-demethoxygeldanamycin Enhances Apoptosis Induced by Oxaliplatin via Suppression of Erk Signaling Pathway in RKO Colon Cancer Cell Line

作　　者：马广友[1] 朱志图[2] 陈明子[2] 王圆圆[2] 王莹[2] 金晓红[2] 丛顺地[2] 李恩泽[2] 

机构地区：[1]辽宁医学院附属第一医院大肠外科,辽宁锦州121001 [2]辽宁医学院附属第一医院肿瘤科,辽宁锦州121001

出　　处：《肿瘤防治研究》2013年第8期752-757,共6页Cancer Research on Prevention and Treatment

基　　金：辽宁省科技厅科学技术计划项目(2011225015);辽宁省教育厅一般项目(L2010277)

摘　　要：目的研究17-AAG与奥沙利铂是否存在协同效应,并探讨PI3K/Akt、Erk信号通路在奥沙利铂联合17-AAG诱导人结肠癌细胞凋亡过程中的作用。方法四甲基偶氮唑盐比色实验(MTT法)检测17-AAG、奥沙利铂对细胞增殖的抑制作用;流式细胞术分析细胞凋亡情况;Western blot法检测相关蛋白的表达水平。结果 17-AAG能抑制RKO细胞的增殖;17-AAG联合奥沙利铂作用于RKO细胞24h后,G2/M期细胞比例及凋亡率明显增加;奥沙利铂抑制p-Akt、p-Erk的活化,上调Bax,下调Bcl-2蛋白表达,活化裂解Caspase-3,联合使用17-AAG后可进一步增强上述作用,但对PI3K/Akt信号通路影响不大。结论本实验表明17-AAG具有增强奥沙利铂诱导结肠癌RKO细胞凋亡的作用,同时也说明17-AAG与奥沙利铂存在协同效应;17-AAG上调Bax,下调Bcl-2蛋白表达及增强奥沙利铂对Erk信号通路的抑制作用可能是其促进凋亡的重要机制之一。Objective To determine whether there was a synergistic effect between the Hsp90 inhibitor 17-AAG and oxaliplatin and to further investigate the roles of PI3K/Akt and Erk in apoptosis induced with 17-AAG and oxaliplatin treatment in a human colon cancer cell line.Methods Colorimetric 3-[4,5-dimethy thiazol-2-yl]-2,5-diphenyl tetrazolium bromide（MTT） assay was used to study the inhibitory effect on proliferation of RKO cell treated with 17-AAG and oxaliplatin,Apoptosis was evaluated by flow cytometry;Western blot was carried out to determine protein expression levels.Results 17-AAG could definitely inhibit the of RKO cells.When the RKO cells were exposed to 17-AAG combined with oxaliplatin for 24 h,G2/M ratio and apoptosis rates were significantly increased.Oxaliplatin significantly decreased the protein expression of p-Akt and p-Erk.Oxaliplatin was also found to significantly increase the protein expression of Bax and Caspase-3 and to decrease the expression of Bcl-2.All these effects were enhanced when identical experiments were carried out in the presence of 17-AAG,but it had no apparent effects on the PI3K/Akt signaling pathway.Conclusion 17-AAG enhances apoptosis induced by oxaliplatin in RKO cells and there maybe exist a synergistic effect between 17-AAG and oxaliplatin.The increased expression of Bax,the decreased expression of Bcl-2 and the inhibition of Erk signaling pathway may be the underlying mechanisms leading to apoptosis.

关 键 词：结肠癌 17-丙烯胺基-17-去甲氧基格尔德霉素 奥沙利铂 凋亡 PI3K Akt ERK 

分 类 号：R735.35[医药卫生—肿瘤]