3-甲基腺嘌呤对蛋白酶体抑制剂MG132抗卵巢癌A2870细胞作用的影响  

The effect of 3-methyladenine on cytotoxicity of ovarian cancer A2870 cells induced by proteasome inhibitor MG132

作　　者：刘川[1] 王华芹[2] 高雁艳[2] 林蓓[1] 

机构地区：[1]中国医科大学附属盛京医院妇产科学教研室,辽宁沈阳110004 [2]中国医科大学基础医学院生物化学与分子生物学教研室,辽宁沈阳110001

出　　处：《现代肿瘤医学》2013年第4期682-685,共4页Journal of Modern Oncology

基　　金：国家自然科学基金资助项目(编号:81172491);高等学校博士学科点专项科研基金资助项目(编号:20112104110016)

摘　　要：目的:研究PI3K通路自噬抑制剂3-甲基腺嘌呤(3-methyladenine,3-MA)对蛋白酶体抑制剂MG132抗卵巢癌A2870细胞作用的影响。方法:不同浓度MG132处理A2870细胞后,MTT法及Annexin V-FITC/PI双染法检测细胞的生存率及凋亡改变,吖啶橙(AO)染色和Western-Blot法检测酸性自噬泡的形成及自噬特异性蛋白LC3的变化。3-MA联合MG132处理A2870细胞,MTT法检测细胞的生存率,AO染色和Western blot法检测自噬的改变。结果:MG132可诱导A2870卵巢癌细胞发生增殖抑制及凋亡,同时,酸性自噬泡形成及LC3-I向LC3-Ⅱ的转化增强。而3-MA联合MG132明显降低A2870细胞的生存率,但不改变MG132诱导的A2870细胞的自噬水平。结论:3-MA对MG132抗A2870卵巢癌细胞的增强作用与自噬无关。MG132诱导A2870细胞发生的自噬与PI3K通路无关。Objective ：To investigate the effect of 3 -methyladenine on cytotoxicity of ovarian cancer A2870 cells induced by proteasome inhibitor MG132. Methods：A2870 cells were treated with different doses of MG132 for 24h, cell viability was assessed by methyl thiazolyl tetrazolium（MT]？） assay ,and apoptosis was observed with Annexin V - FITC and PI double staining followed by flowcytometry. The acidic vesicular organelles were observed using fluores- cent microscope by acridine orange（AO） staining. The transition of autophagy - specific protein LC3 （ microtubule - associated protein 1 light chain 3 ）were detected by Western Blot. A2870 cells were cotreated with MG132 and 3 - MA,cell viability and autophagy were assessed by MTY assay, AO staining and Western Blot. Results： MGI32 suppressed cell viability and induced apoptosis in A2870 cells. MG132 increased accumulation of acidic vacuoles and transition of LC3 -I to LC3 - ]I. 3 -MA enhanced the cytotoxicity of A2870 cells mediated by MG132 ,but demonstrated no obvious effect on autophagy induced by MG132. Conclusion：The enhancement of 3 -MA on cytotoxicity of A2870 cells induced by MG132 was not associated with autophagy. MG132 induced PI3K - independent autophagy in A2870 cells.

关 键 词：蛋白酶体抑制剂 自噬 PI3K 3-甲基腺嘌呤 卵巢癌 

分 类 号：R979.1[医药卫生—药品] R737.31[医药卫生—药学]