Candesartan attenuates angiogenesis in hepatocellular carcinoma via downregulating AT1R/VEGF pathway

Abstract

Angiotensin II type 1 receptor (AT1R) was reported to express in many types of tumors, promoting tumor growth and angiogenesis. We herein examined AT1R expression in liver cancer and the potential antitumor effects of AT1R antagonist Candesartan in liver cancer. We found that AT1R expression was positively correlated with VEGF-A expression and microvascular density (MVD) in 40 HCC patients. Angiotensin II and Candesartan neither had effects on the proliferation of liver cancer cells in vitro. However, Angiotensin II upregulated AT1R protein expression and promoted production of VEGF-A in liver cancer cells in a dose-dependent manner. Candesartan was able to reverse this process in a dose-dependent manner. Moreover, Candesartan downregulated the expression of VEGF-A in SMMC-7721 bearing xenografts in mice and inhibited tumor growth and angiogenesis in vivo. Our data suggested that AT1R antagonist Candesartan might be useful to suppress liver cancer by inhibiting angiogenesis.