华蟾素对人乳腺癌细胞阿霉素多药耐药性的逆转作用

Reversal effect of cinobufacine on adriamycin resistancehuman breast cancer cells

目的以耐阿霉素人乳腺癌细胞系MCF-7/ADM为对象,验证华蟾素(cinobufacine,Cino)能否逆转其对阿霉素(ADM)的耐药性。方法采用MTT法检测药物细胞毒性作用及耐药细胞逆转倍数,高效液相色谱法检测细胞内ADM的浓度,流式细胞术测定P-糖蛋白(permeability glycoprotein,P-gp)的表达。结果Cino15mg·L-1能增加MCF-7/ADM细胞对ADM的敏感性,使ADM的半数抑制浓度(IC50)由38.14mg·L-1降至12.93mg·L-1;能提高ADM在MCF-7/ADM细胞内的浓度,降低MCF-7/ADM细胞P-gp的表达。结论研究表明Cino能部分逆转MCF-7/ADM细胞的MDR,其机制与抑制P-gp的功能与表达,增加细胞内ADM的含量有关。

Aim To investigate the reversal effect of cinobufacine（Cino） on adrimycin （ ADM ） resistant human breast cancer cell line MCF-7/ADM. Methods The cytotoxic effect of Cino or ADM and the sensitivity of ADM to cells was determined by MTT assay. The intracellular concentration of ADM was detected by HPLC. The expression of P-glycoprotein（P-gp） was examined by flow cytometric （FCM） . Results The maximum non-toxic dose Cino（ 15 mg·L^-1） increased the sensitivity of ADM in MCF-7/ADM,decreased the IC50 of ADM in MCF-7/ADM from 38. 14 mg·L^-1 to 12.93mg·L^-1, and significantly increased the intra- cellular concentration of ADM in MCF-7/ADM and re-duced the expression of P-glycoprotein. Condution The results showed that Cino can partially reverse multidrug resistance（MDR） of MCF-7/ADM cells and the mechanism might be associated with the increase of intracellular accumulation of ADM and the reduced expression of P-glycoprotein （P-gp） in MCF-7/ADM cells.