姜黄素水解物对K562/A02细胞多药耐药的逆转作用研究

目的:研究姜黄素水解物对K562/A02细胞多药耐药的逆转作用,初步探讨其逆转机制。方法:MTT法检测姜黄素水解物处理后K562/A02细胞对常用化疗药物敏感性的变化;免疫组织化学法检测姜黄素水解物处理后K562/A02细胞与其亲本K562细胞膜P-gp的表达;流式细胞术检测K562和K562/A02细胞内柔红霉素(DNR)的平均荧光强度(mean fluo-rescene intendity,MFI);RT-PCR法检测K562/A02细胞mdr1 mRNA。结果:用2.5 mg.L-1姜黄素水解物处理后K562/A02细胞对常用化疗药物敏感性提高;姜黄素水解物能降低K562/A02细胞膜P-gp的表达(P0.05)。K562/A02细胞内DNR的MFI低于K562细胞(P0.01),姜黄素水解物能增加K562/A02细胞内DNR的MFI(P0.05);姜黄素水解物处理后K562/A02细胞内mdr1 mRNA下降。结论:姜黄素水解物具有体外逆转K562/A02细胞多药耐药的作用,且降低K562/A02细胞膜P-gp的表达降低化疗药物外排增强化疗药物在细胞内的潴留可能是其逆转作用的机制之一。

Studies on reversing MDR of K562/A02 by ramification of curcumin hydrolyzed

Objective : To determine the reversal effects of ramification of curcumin hydrolyzed on multidrug-resistant cell line K562/A02, and explore its reversal mechanism. Method : After treatment with ramification of curcumin hydrolyzed, the sensitivity of K562/A02 cells to usuall chemotherapeutic drugs were determined by MTT. The expression of P-gp in K562/A02 and K562 cells was detected by immunohistochemical method. Intracellular mean fluorescence intensity (MFI) of DNR in K562 and K562/A02 cells was detected by Flow Cytometry. Result : After treatment with the ramification of curcumin, hydrolyzed (2.5 mg·L^-1) IC₅₀ of usuall chemotherapeutic drugs to K562/A02 decreased. The sensitivity of K562/A02 cells increased. The expression of the P-gp in K562/A02 cells decreased(P<0.05); MFI of the DNR in K562/A02 cells more significantly increased (P<0.05). The expression of mdr1-mRNA decreased. Conclusion : The ramification of curcumin hydrolyzed have effects on the reversal multidrug-resistant of K562/A02 cells in vitro.It could enhance the sensitivity of K562/A02 cells to chemotherapeutic drugs and the mechanism might be associated with inhibiting P-gp-mediated drug efflux and increasing of intracellular concentration of chemotherapeutic drugs.