Sinomenine reverses multidrug resistance in bladder cancer cells via P-glycoprotein-dependent and independent manners
Sinomenine reverses multidrug resistance in bladder cancer cells via P-glycoprotein-dependent and independent manners
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DOI：
10.1619/ph.2014.3722
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发表时间：
2014-01-01
期刊：
影响因子：
1.6
通讯作者：
He, Dalin
中科院分区：
文献类型：
--
作者：
Chen, Yule;Zhang, Linlin;He, Dalin
P-糖蛋白介导的多药耐药是化疗期间的常见事件，也是膀胱癌治疗的关键障碍。寻找逆转多药耐药性的策略是改善膀胱癌治疗的一种有前途的方法。在本研究中，我们报道了一种新型P-糖蛋白介导的多药耐药细胞模型253J/DOX，该模型是从人膀胱癌253J细胞系产生的。此外，我们发现253J/DOX细胞的多重耐药表型可以被青藤碱（一种源自青藤茎的生物碱）克服。从机制上讲，青藤碱的化学敏感性作用是通过下调 P-糖蛋白表达以及触发细胞凋亡途径介导的。青藤碱的化学敏感性作用可能使其成为治疗膀胱癌的主要候选药物。
P-Glycoprotein-mediated multidrug resistance is a frequent event during chemotherapy and a key obstacle for bladder cancer therapy. Search for strategies to reverse multidrug resistance is a promising approach to improve the management of bladder cancer. In the present study, we reported a novel P-glycoprotein-mediated multidrug resistant cell model 253J/DOX, which was generated from human bladder cancer 253J cell line. Furthermore, we found that the multidrug resistant phenotype of 253J/DOX cells could be overcome by sinomenine, an alkaloid derived from the stem of Sinomenium acutum. Mechanistically, the chemosensitive effect by sinomenine was mediated by down-regulating P-glycoprotein expression, as well as triggering apoptotic pathways. The chemosensitive effect of sinomenine may make it a prime candidate agent to target bladder cancer.