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本研究探讨环孢菌素A(CsA)、雌激素受体抑制剂雷洛昔芬及其联合应用对K562/A02细胞多药耐药的逆转作用。采用甲基四唑蓝法(MTT)测定柔红霉素(DNR)的半数抑制量,RT-PCR法检测mdr1基因mRNA表达水平,FCM检测P-gp的表达和细胞内DNR浓度。结果表明:DNR对K562/A02和K562细胞的IC50分别为23.51和0.29mg/L,雷洛昔芬(2.5mg/L)及CsA(1mg/L)单用和两药联合处理K562/A02细胞时,DNR的IC50值分别为5.98、8.15和3.68mg/L,两药对DNR作用K562细胞的IC50没有影响。CsA及雷洛昔芬单独作用后耐药株mdr1mRNA下调微弱,联合用药下调效果明显。CsA及雷洛昔芬均可降低P-gp蛋白的表达,且具有协同作用。同时还观察到逆转剂雷洛昔芬和CsA作用后细胞内柔红霉素浓度增加,两药联合作用时效果增强。结论:CsA及雷洛昔芬均可逆转耐药,且联合作用效果增强。
This study was designed to investigate the reversal effects of cyclosporin A (CsA) and raloxifene combined with its inhibitor on multidrug resistance in K562 / A02 cells. The half inhibition of daunorubicin (DNR) was determined by methyltetrazolium (MTT) assay. The mRNA expression of mdr1 was detected by RT-PCR. The expression of P-gp and the concentration of intracellular DNR were detected by FCM. The results showed that the IC50 of DNR on K562 / A02 and K562 cells were 23.51 and 0.29 mg / L, respectively. Raloxifene (2.5 mg / L) and CsA (1 mg / L) , The IC50 of DNR were 5.98, 8.15 and 3.68 mg / L, respectively. The two drugs had no effect on the IC50 of K562 cells treated with DNR. CsA and raloxifene alone after the drug-resistant mdr1mRNA down weak, combined with the drug significantly reduced. Both CsA and raloxifene can reduce the expression of P-gp protein and have a synergistic effect. At the same time, the intracellular daunorubicin concentration was observed after the reversal agents raloxifene and CsA, and the effect was enhanced when the two drugs were combined. Conclusion: Both CsA and raloxifene can reverse drug resistance, and the combination effect is enhanced.