抑制自噬对乳腺癌阿霉素耐药的逆转作用  

Reversal effect of autophagy inhibition on adriamycin resistance of breast cancer

作　　者：陈平[1] 吴正升[1] 吴强[1] 闫红[1] 汪树静 

机构地区：[1]安徽医科大学病理学教研室,合肥230032

出　　处：《临床与实验病理学杂志》2016年第5期528-532,共5页Chinese Journal of Clinical and Experimental Pathology

基　　金：国家自然科学基金(81472493)

摘　　要：目的探讨自噬在乳腺癌阿霉素耐药过程中发挥的作用。方法采用大剂量阿霉素间歇诱导MCF-7细胞;应用MTT法检测阿霉素耐药细胞株MCF-7/ADM的耐药指数;通过qRT-PCR、Western blot及细胞免疫荧光法检测自噬表达;选用自噬抑制剂3-Methyladenine(3-MA)抑制细胞自噬,并检测MCF-7/ADM细胞株耐药性的逆转情况。结果乳腺癌耐药细胞株MCF-7/ADM成功建立,MCF-7/ADM细胞对ADM有明显的耐药性,阿霉素抑制MCF-7和MCF-7/ADM细胞存活的IC50值分别为1.0 971μg/ml和175.8 921μg/ml,耐药倍数为160(P<0.01),且MCF-7/ADM细胞自噬表达升高,加入3-MA的实验组细胞耐药逆转倍数为1.16,差异有统计学意义(P<0.05)。结论抑制自噬可部分逆转MCF-7/ADM细胞耐药。Purpose To study the effect of autophagy on adriamycin resistance of breast cancer cell. Methods human adriamycin-resistant breast cancer cell line （ MCF-7/ADM ） by high doses of intermittent induction was established. The effect of adriamycin on MCF-7 and MCF-7/ADM cell proliferation inhibition were detected by MTT. Expression of autophagy related homologue mRNA and protein was performed by qRT-PCR and Western blot analysis. The reversal activity of 3-Methyladenine （3-MA） on MCF-7/ADM by MTT was detected. Results Human adriamycin-resistant breast cancer cell line （MCF-7/ADM） was successfully established and verified. The inhibition ratio of MCF-7/ADM cell was higher than MCF-7 and sensitivity of adriamycin of MCF-7/ADM was significantly lower than MCF-7. The ICso values of MCF-7 and MCF-7/ADM cell survival were 1.0 971 p^g/ml and 175.8 921 p^g/ml respectively. The drug resistance fold was 160 （P 〈0. O1 ）. The expression of autophagy markers were increased in MCF-7/ADM. 3-MA could increase the cellular sensitivity to ADM and the drug resistance reversal fold in the experimental groups was 1.16 times （ P 〈 0. 05 ）. Conclusion Inhibition of autophagy can reverse adriamyein resistance in breast cancer cell.

关 键 词：乳腺肿瘤 阿霉素耐药 MCF-7/ADM 自噬 3-Methyladenine 

分 类 号：R737.9[医药卫生—肿瘤]