咯萘啶逆转人乳腺癌MCF-7/ADM细胞耐药性及机制探讨

Reversal effect and mechanism of pyronaridine on drug resistance of breast cancer cell MCF-7/ADM

目的在明确咯萘啶(PND)逆转人乳腺癌细胞MCF-7/ADM耐药性的药效基础上,初步探索作用机制。方法采用MTT法检测单用阿霉素(ADM)和联用咯萘啶(PND)对人乳腺癌敏感细胞MCF-7和耐药细胞MCF-7/ADM的抑制作用,得出半数抑制浓度(IC50),并计算耐药倍数和逆转倍数。Western blot检测细胞中Fas和Caspases-3蛋白表达。结果 ADM对MCF-7和MCF-7/ADM的IC50分别为1.399μg/m L和43.885μg/m L,耐药倍数为31.4倍。PND(0.5μg/m L)联合ADM作用MCF-7/ADM的IC50为3.246μg/m L,逆转倍数为13.5倍,并能提高耐药MCF-7/ADM中Fas和Caspases-3蛋白表达。结论 PND能够逆转人乳腺癌细胞MCF-7/ADM耐药性,通过上调膜蛋白Fas表达,增加MCF-7/ADM对ADM的敏感性,从而促进细胞凋亡。

Objective Based on the effect of pyronaridine （PND） in reversing drug- resistance of human breast cancer cell MCF-7/ADM,to explore the mechanism of action.MethodsThe inhibitory effect of simple adriamycin （ADM） and combined with PND on sensitive human breast cancer cell MCF-7 and drug-resistance MCF-7/ADM was detected by MTT assay,and to calculate median inhibitory concentration,resistance index and reversal index.Cells were designated as MCF-7/ADM group,MCF-7/ADM＋ADM group and MCF-7/ADM＋ADM＋PND group.Western blot detected the expression of Fas and Caspases-3 in cells.ResultsThe IC50 of ADM to MCF-7 and MCF-7/＋ADM were 1.399 μg/mL和43.885 μg/mL,respectively,and the resistance index was 31.4.The IC50 of PND combined with ADM to MCF-7/ADM was 3.246 μg/mL,and the reversal index was 13.5.Compared with MCF-7/ADM group,the expression of Fas and Caspases had no statistic difference （P〉0.05） in MCF-7/ADM ＋ADM group,but the expression increased significantly in MCF-7/ADM ＋ADM＋PND group （P〈0.05）.ConclusionPND could reverse drug- resistance of MCF-7/ADM by up-regulating expression of membrane protein Fas,which increased sensibility of MCF-7/ADM to ADM,and induced the cell apoptosis.