GSK-3 inhibition in vitro and in vivo enhances antitumor effect of sorafenib in renal cell carcinoma (RCC)
GSK-3 inhibition in vitro and in vivo enhances antitumor effect of sorafenib in renal cell carcinoma (RCC)
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DOI：
10.1016/j.bbrc.2012.05.147
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发表时间：
2012-07-06
影响因子：
3.1
通讯作者：
Tomita, Yoshihiko
中科院分区：
文献类型：
--
作者：
Kawazoe, Hisashi;Bilim, Vladimir N.;Tomita, Yoshihiko
索拉非尼是一种多激酶抑制剂，被批准用于肾细胞癌（RCC）的全身治疗。然而，索拉非尼治疗由于RCC的获得性耐药性而具有有限的效果。以前，我们确定糖原合成酶激酶-3（GSK-3）作为肾细胞癌的新治疗靶点。在这里，我们观察到索拉非尼抑制RCC细胞的增殖和存活。值得注意的是，我们发现索拉非尼增强了RCC细胞中GSK-3的活性，这可能是获得性耐药的潜在机制。我们发现GSK-3的药理学抑制增强了索拉非尼在体外和体内的抗肿瘤作用。我们的研究结果表明，GSK-3抑制剂联合索拉非尼可能是一种潜在的治疗肾癌的新方法。(C)2012 Elsevier Inc. All rights reserved.
Sorafenib is a multikinase inhibitor approved for the systemic treatment of renal cell carcinoma (RCC). However, sorafenib treatment has a limited effect due to acquired chemoresistance of RCC. Previously, we identified glycogen synthase kinase-3 (GSK-3) as a new therapeutic target in RCC. Here, we observed that sorafenib inhibits proliferation and survival of RCC cells. Significantly, we revealed that sorafenib enhances GSK-3 activity in RCC cells, which could be a potential mechanism of acquired chemoresistance. We found that pharmacological inhibition of GSK-3 potentiates sorafenib antitumor effect in vitro and in vivo. Our results suggest that combining GSK-3 inhibitor and sorafenib might be a potential new therapeutic approach for RCC treatment. (C) 2012 Elsevier Inc. All rights reserved.