Abstract
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.
Original language | English (US) |
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Pages (from-to) | 490-495 |
Number of pages | 6 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 423 |
Issue number | 3 |
DOIs | |
State | Published - Jul 6 2012 |
Keywords
- Glycogen synthase kinase-3
- Renal cell carcinoma
- Sorafenib
- Tyrosine kinase inhibitor
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Molecular Biology
- Cell Biology