氨氯地平衍生物CJX1对K562/DOX细胞阿霉素耐药的逆转作用  

Reversal of Resistance to Doxorubicin by CJX1,an Amlodipine Derivative,in Doxo rubicin-resistant Human Myelogenous Leukemia (K562/ DOX) Cells

作　　者：姬汴生[1] 何玲[1] 刘国卿[1] 

机构地区：[1]中国药科大学药理学教研室,南京210009

出　　处：《中国药科大学学报》2005年第2期159-163,共5页Journal of China Pharmaceutical University

基　　金：江苏省自然科学基金资助项目 (BK2 0 0 4110 )

摘　　要：目的:研究氨氯地平衍生物CJX1对K5 6 2 /DOX细胞阿霉素耐药的逆转作用。方法:应用流式细胞仪和MTT法观察了CJX1对K5 6 2 /DOX细胞P- 糖蛋白(P -gp)的抑制作用及对K5 6 2 /DOX细胞阿霉素耐药的逆转作用。结果:CJX1能剂量相关性地增加K5 6 2 /DOX细胞内罗丹明12 3(Rh 12 3)的累计,明显抑制P -gp介导的Rh 12 3外排,显著增强阿霉素对K5 6 2 /DOX细胞的细胞毒作用,增加K5 6 2 /DOX细胞内阿霉素水平。结论:氨氯地平衍生物CJX1能显著抑制P gp的外排功能,逆转K5 6 2 /DOX细胞的多药耐药性。AIM:To study the reversal of resistance to doxoru bi cin by CJX1,an amlodipine derivative, in doxorubicin-resistant human myelogen o us leukemia(K562/DOX)cells.METHOD:The effect of CJX1 on P-glyco protein function and resistance to doxorubicin in K562/ DOX cells was explored by using flo w cytometric technology and MTT assay.RESULT:CJX1 increased intr acellular accumulation of rhodanmine 123 (Rh 123)in K562/DOX cells in a dose-de pendent manner and significantly inhibited the efflux of Rh 123 from the cells. The doxoru b icin-induced cytotoxicity and apoptosis were significantly potentiated by CJX1 by promoting intracellular doxorubicin.CONCLUSION:The reversed ef fect of CJX1 on multidrug resistance to doxorubicin in K562/ DOX cells could be atlributed to CJX1's inhibitory effect on P-glycoprotein function.

关 键 词：CJX1 氨氯地平衍生物 P-糖蛋白 多药耐药 阿霉素 逆转作用 

分 类 号：R965[医药卫生—药理学]