雄黄与β-榄香烯联合用药逆转MCF-7/ADM细胞对阿霉素耐药性的研究

REVERSAL OF RESISTANCE TO ADRIAMYCIN IN MCF-7/ADM CELLS BY REALGAR IN COMBINATION WITH β-ELEMENE

目的探讨不同作用机制的雄黄(REA)与β-榄香烯(β-ELE)联合应用,从不同环节逆转人乳腺癌MCF-7/ADM细胞对阿霉素(ADM)的耐药性。方法联合用药后,经MTT法测定对MCF-7/ADM细胞药物敏感性的影响,通过荧光分光光度法检测对细胞内化疗药物阿霉素积累的影响,应用流式细胞术检测P-GP、Bcl-2蛋白表达的改变。结果联合用药对MCF-7/ADM的耐药性有明显的逆转作用,逆转倍数约为4.2倍,明显好于两者单独应用(P<0.01)。联合用药后,MCF-7/ADM细胞内阿霉素浓度明显增加(P<0.01),P-GP表达由(95.90±3.02)%降至(76.50±5.16)%(P<0.01),Bcl-2表达由(90.20±3.99)%降至(50.00±1.63)%(P<0.01)。结论雄黄与β-榄香烯联合用药可显著增强对MCF-7/ADM细胞的耐药逆转作用,逆转机制与增加细胞内药物积累,降低P-GP、Bcl-2的表达有关。

Objective To study the reversal effect of adriamycin （ADM） resistance in human breast cancer cell line MCF-7/ADM by realgar （REA） combined with β-elemene （β-ELE）, two types of anticancer drugs. Methods The sensitivity to ADM of MCF-7/ADM cells was studied by MTT assay .The intracellular accumulation of ADM in MCF-7/ADM cells was observed by fluorescent-spectrophotometry. Expressions of P-GP protein and Bcl-2 protein were detected by flow cytometry. Results The combined treatment of REA and β-ELE could significantly enhance the cytotoxic effect of ADM on MCF-7/ADM cells to 4.2 fold as compared with the treatment of PEA or β-ELE respectively （ P 〈 0.01 ）. The intracellular accumulation of ADM in MCF-7/ADM cells was significantly increased after the combined treatment （P 〈 0.01 ）. The expression of P-Gp protein in MCF-7/ADM cells was reduced from（95.90 ± 3.02） % to （76.50 ± 5.16） % （ P 〈 0.01 ） while the expression of Bcl-2 protein was reduced from （90.20 ± 3.99） % to （50.00 ± 1.63） % （ P 〈 0.01 ）. Conclusion The combined treatment of PEA and β-ELE could reverse more strongly the drug resistance to ADM in MCF-7/ADM cells, which is related to the increased accumulation of intracellular ADM and the decreased expression of P-GP and Bcl-2.