Multidrug Resistance Protein 2 Implicates Anticancer Drug-Resistance to Sorafenib
Multidrug Resistance Protein 2 Implicates Anticancer Drug-Resistance to Sorafenib
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DOI：
10.1248/bpb.34.433
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发表时间：
2011-03-01
影响因子：
2
通讯作者：
Yamada, Katsushi
中科院分区：
文献类型：
--
作者：
Shibayama, Yoshihiko;Nakano, Kou;Yamada, Katsushi
索拉非尼和舒尼替尼是某些受体酪氨酸激酶的小分子抑制剂，并改善了晚期肾细胞癌患者的预后。与对照细胞系相比，索拉非尼在多药耐药蛋白2（MRP 2）转染细胞系中的50%细胞生长抑制浓度显著升高至6.4倍。索拉非尼的浓度在处理3小时后显著降低至对照细胞的74%。相反，酪氨酸激酶抑制剂舒尼替尼未显示50%细胞生长的抑制浓度的改变和向MRP2转染细胞的细胞中的蓄积。目前的研究表明，索拉非尼是MRP2的底物，这表明MRP2可能与索拉非尼耐药有关。
Sorafenib and sunitinib is a small molecule inhibitor of certain receptor tyrosine kinases, and have improved outcomes for patients with advanced renal cell carcinoma. Inhibitory concentration of 50% cell growth of sorafenib significantly rose to 6.4-fold in a multidrug resistance protein 2 (MRP2) transfected cell line versus control cell line. The concentration of sorafenib was significantly decreased to 74% of control cells after 3 h treatment. In contrast, a tyrosine kinase inhibitor sunitinib did not show alteration of inhibitory concentration of 50% cell growth and accumulation into the cells of MRP2 transfected cells. The present study suggest that sorafenib is a substrate for MRP2, suggesting that MRP2 may implicate drug resistance to sorafenib.