Education Research Center for Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060–0812, Japan.
Biol Pharm Bull. 2011;34(3):433-5. doi: 10.1248/bpb.34.433.
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.
索拉非尼和舒尼替尼是一种小分子抑制剂，可抑制某些受体酪氨酸激酶，可改善晚期肾细胞癌患者的预后。在多药耐药蛋白 2（MRP2）转染的细胞系中，索拉非尼的抑制浓度为 50％细胞生长的 6.4 倍，明显高于对照细胞系。与对照细胞相比，索拉非尼处理 3 小时后，浓度降低至对照细胞的 74％。相比之下，一种酪氨酸激酶抑制剂舒尼替尼并未显示出 50％细胞生长抑制浓度的改变，也没有将其蓄积到转染的 MRP2 细胞中。本研究表明索拉非尼是 MRP2 的底物，提示 MRP2 可能与索拉非尼的耐药性有关。
