阿霉素通过Stat3-cMyc途径诱导三阴性乳腺癌MDA-MB-468细胞耐药性  

Adriamycin Induced Chemoresistance of Human TNBC MDA-MB-468 Cells Through Stat3-cMyc Signal Pathway

作　　者：徐金媛 成丛丛 钟瑾怡 崔镓钰 张宝刚[4] 王丽华[2] 孙秀宁[5] 史立宏 XU Jinyuan;CHENG Congcong;ZHONG Jinyi;CUI Jiayu;ZHANG Baogang;WANG Lihua;SUN Xiuning;SHI Lihong(Department of Pharmacy,Weifang Medical University,Weifang 261053,China;Laboratory of Molecular Oncology,Affiliated Hospital,Weifang Medical University,Weifang 261053,China;School of Clinical Medicine,Weifang Medical University,Weifang 261053,China;Department of Pathology,Weifang Medical University,Weifang 261053,China;Department of Pathogeny Microbiology,Weifang Medical University,Weifang 261053,China)

机构地区：[1]潍坊医学院药学院,潍坊261053 [2]潍坊医学院附属医院分子肿瘤学实验室,潍坊261053 [3]潍坊医学院临床医学院,潍坊261053 [4]潍坊医学院病理学教研室,潍坊261053 [5]潍坊医学院病原微生物学教研室,潍坊261053

出　　处：《肿瘤防治研究》2018年第12期949-953,共5页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金(81672631;81472489);山东省自然科学基金(ZR2015HL119;ZR2011HL047);山东省政府公派留学项目;潍坊医学院留学项目

摘　　要：目的观察阿霉素(Adriamycin,ADM)对人三阴性乳腺癌MDA-MB-468细胞耐药性的诱导作用并探讨其机制。方法培养人三阴性乳腺癌MDA-MB-468细胞,用不同浓度阿霉素处理细胞24 h后,MTT法检测细胞生长抑制率及细胞对阿霉素的敏感度。免疫荧光染色法检测耐药蛋白ABCG2的表达;免疫印迹法检测Stat3、p-Stat3、转录因子cMyc及耐药蛋白ABCG2的表达水平。结果阿霉素持续刺激4周后,获得的MDA-MB-468/ADM细胞对阿霉素的敏感度明显降低,且耐药蛋白ABCG2的表达明显增加;MDA-MB-468/ADM细胞p-Stat3、cMyc及ABCG2的表达量显著增加;MDAMB-468/ADM细胞培养液中加入WP1066后Stat3磷酸化明显抑制,cMyc及ABCG2的表达水平下调,并且MDA-MB-468/ADM细胞对阿霉素的敏感度明显增强(P<0.05)。结论阿霉素可以通过Stat3-cMyc途径诱导三阴性乳腺癌MDA-MB-468细胞产生耐药性。Objective To investigate the chemoresistance of human triple-negative breast cancer(TNBC)MDA-MB-468 cells induced by adriamycin(ADM)and the underlying mechanism.Methods MDA-MB-468 cells were treated with ADM at different concentrations for 24h,then MTT assay was used to detect the inhibitory rate of cell growth and the sensitivity of MDA-MB-468 cells to ADM.Immunofluorescence staining was used to detect the expression level of ABCG2 and Western blot was used to test the expression levels of phosphorylated Stat3(p-Stat3),cMyc and ABCG2.Results The sensitivity of MDA-MB-468/ADM to ADM was remarkably reduced and the expression of drug resistance protein ABCG2 was increased obviously in MDA-MB-468/ADM cells.In addition,the expressions of p-Stat3,cMyc and ABCG2 were much higher in MDA-MB-468/ADM cells than those in MDA-MB-468 cells.Interestingly,when the phosphorylation of Stat3 was inhibited by WP1066,the expressions of cMyc and ABCG2 were downregulated;furthermore,the sensitivity of MDA-MB-468/ADM cells to ADM was increased(P<0.05).Conclusion ADM could induce the chemoresistance of human TNBC MDA-MB-468 cells through Stat3-cMyc signal pathway.

关 键 词：三阴性乳腺癌 阿霉素 耐药性 STAT3 CMYC ABCG2 

分 类 号：R737.9[医药卫生—肿瘤]