苦参碱与粉防己碱逆转人MCF-7细胞耐药性的作用与机制

目的:探讨中药有效成分苦参碱与粉防己碱合用能否逆转人乳腺癌MCF-7细胞的多药耐药性.方法:使用人乳腺癌MCF-7和耐多柔比星的MCF-7/DOX细胞进行研究.采用MTT法检测药物对细胞增殖的影响；流式细胞术检测罗丹明123荧光强度的变化；Western blot方法检测P-糖蛋白的表达变化.结果:苦参碱作用耐药和敏感细胞的IC50相近,耐药细胞对苦参碱没有明显的交叉耐药性；流式细胞术分析发现苦参碱单独处理MCF-7/DOX耐药细胞,可以微弱地降低其耐药性,并且与粉防己碱有协同作用；苦参碱与多柔比星合用,可以增加多柔比星对MCF-7/DOX耐药细胞的生长抑制作用,且与粉防己碱有协同作用；苦参碱和粉防己碱、多柔比星合用处理细胞,MCF-7/DOX耐药细胞株P-糖蛋白表达水平下降.结论:苦参碱与粉防己碱合用具有协同作用,能逆转人乳腺癌MCF-7细胞的多药耐药性,降低P-糖蛋白的表达.

Mechanism of Combination of Matrine and Tetrandrine for Reversal of Multidrug Resistance of Breast Carcinoma MCF-7 Cells

Objective: To investigate the mechanism of combination of matrine and tetrandrine for reversal of multidrug resistance of breast carcinoma MCF-7 cells. Method: Human breast carcinoma MCF-7 and doxorubicin-resistant MCF-7/DOX cells were treated with matrine, tetrandrine and doxorubicin. The inhibition of drugs on cell proliferation was detected by MTT assays. The fluorescence intensity of Rho123 was detected by flow cytometry. The expression of P-glycoprotein was examined by Western blot. Result: The IC₅₀value of matrine toward MCF-7/DOX cell lines was similar to that of MCF-7 cells, indicating that the former has non-cross resistance to matrine. Flow cytometry analysis not only showed matrine reverse multi-drug resistance on MCF-7/DOX, but also has synergy effect with tetrandrine. The cell proliferation inhibition of doxorubicin was obviously increased when the combination of matrine with tetrandrine. Furthermore, reduction of P-glycoprotein expression was detected in MCF-7/DOX cells after exposure to matrine or combination with tetrandrine. Conclusion: Matrine has synergy effect with tetrandrine on reversal of multidrug resistance and reduction of P-glycoprotein expression in breast carcinoma MCF-7 cells.