青蒿素对乳腺癌多药耐药MCF-7/ADR细胞的逆转作用

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。

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

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(P<0.05),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(P>0.05).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.