摘要
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 aimed to investigate the reversible effect of cyclosporine A, raloxifene and their combination on multidmg resistance cell line K562/A02. The IC50 (the concentration causing 50% inhibition of cell growth) of DNR were assayed by MTT method, the expression level of mdr-1 mR.NA was assayed by RT-PCR, p-glycoprotein (P- gp) expression and intracellular DNR concentration were detected by flow cytometry. The results showed that the IC50 of DNR on K562/A02 and K562 cells were 23.51 mg/L and 0.29 mg/L, respectively. The IC50 of DNR on K562/A02 cells in treatment with raloxifene CsA and both combination were 5.98,8.15 and 3.68 mg/L respectively, but both drugs not influenced IC50 of DNR on K562 cells. Pretreating K562/A02 cells with raloxifene (2.5 mg/L) or CsA ( 1 mg/L) for 48 hours partially restored the sensitivity of K562/A02 cells to DNR. Cyclosporine A and raloxifene (alone or combination) elevated the intracellular DNR concentration in K562/A02, down regulated P-gp and mdr-1 mRNA expressions. It is concluded that multidrug resistance (MDR) can be partially reversed by CsA or raloxifene, the combination of both drugs shows a great synergistic reversal effect.
出处
《中国实验血液学杂志》
CAS
CSCD
2006年第5期895-899,共5页
Journal of Experimental Hematology
基金
国家自然科学基金资助(39970832)
省科技发展计划(社会发展)BS20020224