Combined targeting of AKT and mTOR synergistically inhibits proliferation of hepatocellular carcinoma cells.

Abstract

Due to the frequent dysregulation of the PI3K/AKT/mTOR signaling pathway, mTOR represents a suitable therapeutic target in hepatocellular carcinoma (HCC). However, emerging data from clinical trials of HCC patients indicate that mTOR inhibition by RAD001 (Everolimus) alone has only moderate antitumor efficacy which may be due to the feedback activation of AKT after mTOR inhibition. In this study, we analyzed the effects of dual inhibition of mTOR and AKT on the proliferation of HCC cell lines. In addition, we measured the feedback activation of each of the AKT isoforms after mTOR inhibition in HCC cell lines and their enzymatic activity in primary samples from HCC patients.

Bibliografische Daten

OriginalspracheEnglisch
ISSN1476-4598
DOIs
StatusVeröffentlicht - 2012
pubmed 23167739