摘要
目的检测载脂蛋白A-Ⅱ(apolipoprotein A-Ⅱ,APOA-Ⅱ)与阿霉素(adriamycin,ADM)耐药的相关性。方法 IC_(50)分析细胞对ADM的敏感性;激光共聚焦检测MCF7/W细胞、MCF7/ADM细胞及APOA-Ⅱ高表达的MCF7/W细胞内ADM的分布;RT-PCR和Western blot分别检测MCF7/W和MCF7/ADM细胞内APOA-Ⅱ基因及蛋白的表达;IC_(50)分析高表达APOA-Ⅱ的HEK293细胞的药敏性以及高表达APOA-Ⅱ的乳腺癌细胞T47D、MDA-MB231的药敏性。结果MCF7/ADM细胞与MCF7/W细胞相比,耐药指数达13.0(P<0.05);MCF7/W细胞中的ADM在细胞核中大量聚集,而MCF7/ADM细胞中ADM则几无细胞核分布;同时,高表达APOA-Ⅱ蛋白的MCF7/W细胞,其细胞核中ADM的分布明显少于正常表达APOA-Ⅱ的MCF7/W细胞;MCF7/ADM细胞中APOA-Ⅱ的基因及蛋白表达水平均高于亲本细胞(P<0.05);转染了APOA-Ⅱ的HEK293细胞对ADM的敏感性明显降低(P<0.05);并且转染了APOA-Ⅱ的乳腺癌细胞T47D、MDA-MB231对ADM的药敏性也降低(P<0.05)。结论APOA-Ⅱ蛋白与乳腺癌ADM耐药相关,为临床ADM的化疗提供了一定的指导意义。
Aim To study the relationship between apolipoprotein A-Ⅱ（ APOA-Ⅱ） and adriamycin resistance. Methods The drug sensitivity of cells was analyzed by IC_（50） assay. The localizations of ADM in MCF7/W,MCF7/ADM and APOA-Ⅱ transgenic cells were observed by laser scanning confocal microscopy.RT-PCR and Western blot were applied to detect the gene and protein expression in MCF7/W and MCF7/ADM cells,respectively. The APOA-Ⅱ transgenic HEK293 cells were analyzed by IC_（50） assay,the IC_（50） of breat cancer cells T470 and MDA-MB231 were analysed as well. Results Compared with MCF7/W cells,the resistance index of MCF7/ADM cells got 13.0（ P〈 0. 05）. ADM localized mainly in the nuclei of MCF7/W cells,but none in the nuclei of MCF7/ADM cells. Meanwhile,the localization of ADM in APOA-Ⅱtransgenic MCF7/W cells was obviously less than that in normal parent MCF7/W cells. The gene and protein expression levels of APOA-Ⅱ in MCF7/ADM cells were both higher than in MCF7/W cells（ P〈 0. 05）;the sensitivity of APOA-Ⅱ transgenic HEK293 to ADM was also reduced（ P 〈0. 05）. Furthermore,the sensitivity of breast cancer cells T47 D and MDA-MB231 to ADM was reduced as well（ P 〈0. 05）. Conclusion APOA-Ⅱ is found to be positively related to ADM resistance,which would provide instruction for the clinical usage of ADM.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2018年第3期331-336,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金国际(地区)合作与交流项目(No81361168001)
