青蒿素对乳腺癌多药耐药MCF-7/ADR细胞的逆转作用

Reversal of Drug Resistance in Multidrug-resistant MCF-7/ADR Cells of Breast Cancer by Artemisinin

目的探讨青蒿素在乳腺癌多药耐药中的应用。方法采用MTT法观察青蒿素联合阿霉素(ADR)对乳腺癌耐药株MCF-7/ADR细胞生长增殖的影响;应用流式细胞技术测定青蒿素联合ADR对MCF-7/ADR细胞P-糖蛋白(P-glycoprotein,P-gp)表达的影响。结果 10、20、40μmol/L青蒿素实验组的细胞耐药逆转倍数分别为1.53、1.90和3.62倍。青蒿素联合ADR可抑制MCF-7/ADR细胞膜P-gp蛋白的表达,0、10、20、40μmol/L青蒿素作用后的细胞表面P-gp表达阳性率分别为(33.41±4.63)%、(23.07±5.48)%、(21.82±3.87)%和(16.62±1.27)%,组间比较差异均有统计学意义(均P<0.05);各组细胞内总P-gp的表达水平分别为(37.19±5.16)%(、35.30±4.77)%(、37.45±5.19)%和(34.98±3.50)%,各组间差异无统计学意义(P>0.05)。结论青蒿素与ADR同共作用于MCF-7/ADR细胞,使细胞对ADR的敏感性增高,青蒿素具有部分逆转MCF-7/ADR细胞耐药的作用,其逆转作用机制可能是通过影响细胞质和细胞膜之间的P-gp交换,降低细胞膜上P-gp表达水平,提高药物在细胞内的聚集,增强药物对肿瘤细胞的杀伤作用。

Objective To investigate the application of Artemisinin in multidrug resistance of breast cancer.Methods The effects of Artemisinin combined with adriamycin on growth and proliferation of MCF-7/ADR cells were observed by using MTT assay.The expression levels of P-gp in MCF-7/ADR cells treated with Artemisinin plus adriamycin were detected by flow cytometry.Results Artemisinin of 10,20 and 40 μmol/L could induce reversal of drug resistance with the reversal index being 1.53,1.90 and 3.62 times respectively.The positive expression rate of P-gp on the surface of MCF-7/ADR cells treated with Artemisinin（0,10,20 and 40 μmol/L）was（33.41±4.63）%,（23.07±5.48）%,（21.82±3.87）%,（16.62±1.27）% respectively with the difference being significant among groups（P0.05）,and the total expression level of P-gp in cells was（37.19±5.16）%,（35.30±4.77）%,（37.45± 5.19）%,（34.98±3.50）% respectively with the difference being not significant among groups（P0.05）.Conclusion Artemisinin can enhance the effect of adriamycin on MCF-7/ADR cells,indicating Artemisinin can partially induce reversal of multidrug resistance probably by influencing the exchange of P-gp between cytoplasm and cytomembrane,attenuating the expression of P-gp on cytomembrane,promoting the aggregation of adriamycin in cytoplasm and enhancing the killing effect of medicine on tumor cells.