广东药学院学报2012，Vol.28Issue(2)：183-187,5.DOI:10.3969/j.issn.1006-8783.2012.02.021
西地那非和伐地那非逆转MRP7介导的紫杉醇耐药
Sildenafil and vardenafil reverse MRP7-mediated drug resistance to paclitaxel
摘要
Abstract
Objective Previously, we had shown that sildenafil and vardenafil could reverse P-gp-mediated muln'drug resistance (MDR) in vitro. This study was designed to determine whether PDE5 inhibitors have the potential to reverse MRP7-mediated chemotherapeutic drug resistance. Methods The MTT assay was used to access cytotoxicity. The intracellular accumulation of [3H]-paclitaxel was measured in liquid scintillation analyzer. Western blotting was used to determine the MRP7 protein expression. Results Sildenafil, vardenafil and tadalafil at 5 μmol/L significantly increased the sensitivity of HEK-MRP7 cells to paclitaxel by 9. 8-,10.7-and 1. 8-fold, respectively. Consistent with the cytotoxicity results, the drug accumulation data indicated sildenafil,vardenafil and tadalafil at 5 μmol/L significantly enhanced the intracellular accumulation of [3H]-paclitaxel in HEK-MRP7 cells by 3.0-.3.3- and 1.8-fold,respectively. The reversal efficacy of tadalafil was weaker than that of sildenafil and vardenafil. Western blot analysis indicated that sildenafil and vardenafil did not alter the expression of MRP7. Conclusion Sildenafil and vardenafil significantly enhanced the cytotoxicity of paclitaxel to HEK-MRP7 cells through inhibition of the drug efflux function of MRP7 rather than alteration of the expression of MRP7.关键词
西地那非/伐地那非/MRP7/多药耐药/紫杉醇Key words
sildenafil/ vardenafil/ MRP7/ MDR/ paclitaxel分类
药学引用本文复制引用
陈俊江,孙月丽,肖芷洁,陈哲生,陈思东..西地那非和伐地那非逆转MRP7介导的紫杉醇耐药[J].广东药学院学报,2012,28(2):183-187,5.基金项目
广州市科技局国际合作项目(2011J5200017) （2011J5200017）
