新的四氢异喹啉类化合物CPUE1逆转K562/A02细胞的多药耐药性  

Reversal of multidrug resistance by CPUE1 in K562/A02 cells

作　　者：祝浩杰[1] 后媛媛[1] 刘国卿[1] 

机构地区：[1]中国药科大学药理教研室

出　　处：《中国临床药理学与治疗学》2004年第5期544-547,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的 :研究新的四氢异喹啉类化合物CPUE1逆转K5 6 2 A0 2细胞多药耐药性的作用及机制。方法 :在CPUE1的作用下 ,用MTT法检测长春新碱(vincristine ,VCR)对K5 6 2 A0 2多药耐药细胞的细胞毒作用的变化 ,使用DNA分析和Annexin Ⅴ PI双染法研究CPUE1对VCR诱导K5 6 2 A0 2细胞凋亡的影响 ,流式细胞仪检测CPUE1对P 糖蛋白 (P glycop rotein ,P gp)外排罗丹明 12 3(rhodamine12 3,Rh12 3)的作用。结果 :CPUE1能明显提高VCR对K5 6 2 A0 2多药耐药细胞的细胞毒作用以及凋亡诱导作用 ,10 μmol·L-1的CPUE1能使K5 6 2 A0 2对VCR的IC50值由 6 0 .5 4μmol·L-1降至 4 .17μmol·L-1。CPUE1还能抑制Rh12 3外排从而增加细胞内Rh12 3的蓄积浓度。结论 :CPUE1通过抑制P gp的活性逆转K5 6 2 A0 2细胞的多药耐药性。AIM: To study the effect of CPUE1 on the reversal of multidrug resistance (MDR) in K562/A02 cells and its mechanism. METHODS: MTT assay was used to determine the influence of CPUE1 on the cytotoxicity of vincrisine (VCR) in K562/A02 cells. The effect of CPUE1 on the apoptosis induced by VCR in K562/A02 cells was detected using DNA analysis and Annexin-Ⅴ/PI double stain assay. Flow cytometry was used to investigate the efflux of rhodamine123 (Rh123) by P-glycoprotein (P-gp) in K562/A02 cells. RESULTS: CPUE1 increased the cytotoxicity and apoptosis induced by VCR in K562/A02 cells. At the concentration of 10 μmol·L -1 ,CPUE1 reduced the IC_ 50 value of VCR from 60.54 to 4.17 μmol·L -1 . CPUE1 inhibited the efflux of Rh123 and resulted in the increase of intracellular accumulation of Rh123 in K562/A02 cells. CONCLUSION: CPUE1 has strong reversal effect on MDR in K562/A02 cells by inhibiting P-gp activity.

关 键 词：CPUE1 长春新碱 P-糖蛋白 凋亡 多药耐药性 

分 类 号：R966[医药卫生—药理学]