GSK-3 inhibition in vitro and in vivo enhances antitumor effect of sorafenib in renal cell carcinoma (RCC)

Hisashi Kawazoe, Vladimir N. Bilim, Andrey V. Ugolkov, Kaori Yuuki, Sei Naito, Akira Nagaoka, Tomoyuki Kato, Yoshihiko Tomita*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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 languageEnglish (US)
Pages (from-to)490-495
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume423
Issue number3
DOIs
StatePublished - 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

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