青蒿琥酯逆转Eca109/ABCG2细胞对阿霉素耐药的作用及机制

摘要

Objective To explore the effect and mechanism of artesunate (Art) in reversal of resistance of Eca109/ABCG2 cells, an esophageal multidrug resistant cell line, against adriamycin (ADM) . Methods The inhibition of proliferation rate of Eca109/ABCG2 cells was detected by MTT after being treated with Art (0, 0.01, 0.1, 1μmol/L), ADM (0, 0.02, 0.2, 2.20mg/L) , or both Art (0.01,0.1, 1μmol/L) and ADM (0.02,0.2, 2.20mg/L) for 48 hours. After being treated with ADM (0, 0.02, 0.2, 2mg/L), Art (0, 0.01,0.1, 1μmol/L) or both ADM (0.2mg/L) and Art (0. 01, 0. 1, 1μmo/L), the apoptosis rate and the intracellular ADM concentration of Eca109/ABCG2 cells were detected at hour 48, and the expression of ABCG2 protein was detected at hour 72 with flow cytometry (FCM).Results The inhibited proliferation rate, apoptosis rate and intracellular concentration of ADM increased significantly (P＜0.05), and the expression of ABCG2 protein declined notably in cells treated with both Art and ADM than in cells treated with Art or ADM alone.Conclusion Art may reverse the resistance of Eca109/ABCG2 against ADM and enhance the therapeutic effects by down- regulating the expression of ABCG2 protein and increasing the cellular effective concentration of ADM.%目的 研究青蒿琥酯(Art)逆转食管癌耐药细胞Eca109/ABCG2对阿霉素(ADM)耐药的作用及其机制.方法 采用不同浓度的青蒿琥酯(Art,0、0.01、0.1、1μmol/L),阿霉素(ADM,0、0.02、0.2、2、20mg/L),Art(0.01、0.1、1μmol/L)+ADM(0.02、0.2,2、20mg/L)处理Eca109/ABCG2细胞48h,然后以MTT法检测细胞生长抑制率.采用ADM(0、0.02、0.2、2mg/L),Art(0、0.01、0.1、lμmol/L)和ADM(0.2mg/L)+Art(0.01、0.1、μmol/L)处理细胞,48h后以流式细胞术(FCM)检测细胞凋亡率及细胞内ADM含量,72h后检测细胞内ABCG2蛋白的表达.结果 与单独应用Art或ADM相比,Art+ADM处理后,Eca109/ABCG2细胞的生长抑制率、凋亡率和细胞内ADM含量均显著增加(P<0.05),而细胞内ABCG2蛋白表达显著降低(P<0.05).结论 Art可通过下调Eca109/ABCG2细胞ABCG2蛋白表达,增加细胞内ADM的药物浓度,从而增强疗效、逆转耐药.