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. Copyright © 2012 Elsevier Inc. All rights reserved.
Written by:
Kawazoe H, Bilim VN, Ugolkov AV, Yuuki K, Naito S, Nagaoka A, Kato T, Tomita Y Are you the author?
Laboratory of Molecular Oncology, Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990-9585, Japan
Reference: Biochem Biophys Res Commun. 2012 Jul 6;423(3):490-5
PubMed Abstract
PMID: 22683636
UroToday.com Investigative Urology Section
