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

徐金媛; 成丛丛; 钟瑾怡; 崔镓钰; 张宝刚; 王丽华; 孙秀宁; 史立宏

doi:10.3971/j.issn.1000-8578.2018.18.0497

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

摘要

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；MDA-MB-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。

Abstract:
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.

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