Mechanism of action and efficacy of LY2109761, a TGF-β receptor inhibitor, targeting tumor microenvironment in liver cancer after TACE

Abstract

TACE (transcatheter arterial chemoembolization) has been recognized as an effective palliative treatment option for patients with HCC, however, the medium-long term efficacy of it remains modest. LY2109761, a TGF-β receptor inhibitor, was confirmed to reduce tumor cell growth, intravasation, and metastatic dissemination of HCC cells through different molecular mechanisms. This study aims to investigate the treatment effect of combining TACE therapy with LY2109761- a TGF-β receptor I kinase inhibitor on suppressing tumor growth and metastasis in a rabbit VX2 tumor model. The molecular mechanisms underlying the biological activities of LY2109761 was also evaluated through an in vitro model. And we found that LY2109761 could inhibit cell proliferation by down-regulating the phosphorylation of Smad-2 as well as improved the therapeutic effect of TACE in a VX2 hepatocellular carcinoma model. And we further found that LY2109761 may play a modulating role in the process of T cell transformation. Hence, based on those obsevations in our research, we concluded that combing LY2109761 with TACE for the treatment of VX2 rabbit liver cancer can help inhibit tumor growth as well as increase the tumor cell necrosis after TACE.