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目的:探讨汉防己甲素(TTD)、雷洛昔芬及其联合应用对人肝癌多药耐药细胞株Hep-3B/ADM耐药性的逆转作用。方法:通过阿霉素(ADM)浓度梯度递增诱导法,建立人肝癌多药耐药细胞株Hep-3B/ADM。MTT法检测细胞对化学疗法药物的敏感性;流式细胞仪检测P-gp的表达及细胞内ADM强度。结果:ADM对Hep-3B和Hep-3B/ADM细胞的IC50分别为0.059μg/ml和2.131μg/ml,雷洛昔芬(4.90μmol/L)及TTD(1.00μmol/L)单用和两药联合处理Hep-3B/ADM细胞时,ADM的IC50值分别为0.234μg/ml、0.168μg/ml、0.096μg/ml。TTD及雷洛昔芬可降低耐药细胞株P-gp蛋白的表达,且联用有增强效果,同时还观察到逆转剂雷洛昔芬和TTD作用后细胞内阿霉素浓度增加,两药联合作用时效果增强。结论:TTD及雷洛昔芬均可逆转耐药,且联合作用效果增强。
Objective: To investigate the reversal effects of tetrandrine (TTD), raloxifene and their combination on multidrug resistance in human hepatocellular carcinoma cell line Hep-3B / ADM. Methods: Multidrug-resistant human hepatocellular carcinoma cell line Hep-3B / ADM was established by increasing the concentration gradient of adriamycin (ADM). The sensitivity of cells to chemotherapeutic drugs was detected by MTT assay. The expression of P-gp and the intensity of intracellular ADM were detected by flow cytometry. Results: The IC50 of ADM on Hep-3B and Hep-3B / ADM cells were respectively 0.059μg / ml and 2.131μg / ml, raloxifene 4.90μmol / L and TTD 1.00μmol / L, IC50 values of ADM were 0.234μg / ml, 0.168μg / ml and 0.096μg / ml when Hep-3B / ADM cells were treated with drugs. TTD and raloxifene can reduce the expression of P-gp protein in drug-resistant cell line, and combined with enhanced effect, but also observed the reversal agent raloxifene and TTD increased intracellular doxorubicin concentration, two drugs Joint effect of enhanced effect. Conclusion: Both TTD and raloxifene can reverse the drug resistance, and the combination effect is enhanced.