Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth thr
June 27th, 2008 | by admin |Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis.
Since hepatocellular carcinoma (HCC) is a hypervascular cancer, anti-angiogenic therapy is a promising approach to treat HCC. In the present study, we investigated the antiangiogenic and antitumor effects of tum-1, a fragment of tumstatin, gene transduction into HCC in vitro and in vivo. Tum-1 gene was cloned into a pSecTag2B mammalian expression vehicle to construct pSecTag2B-tum-1. pSecTag2B-tum-1 or vehicle were transfected into human HCC cells, PLC/PRF/5 cells stably and Huh-7 cells tran-siently. pSecTag2B-tum-1 transfection slightly repressed the proliferation of both PLC/PRF/5 and Huh-7 cells in vitro. Addition of conditioned media (CM) from tum-1 expressing PLC/PRF/5 cells significantly inhibited the spontaneous and vascular endothelial growth factor (VEGF)-induced proliferation and migration of human umbilical vein endothelial cells (HUVEC) in vitro with diminishing the VEGF-induced phosphorylation of both Akt and extracellular signal-regulated kinase (ERK) that are known to mediate VEGF-induced proliferation and migration of endothelial cells. In in vivo experiments, intratumoral injection of pSecTag2B-tum-1 significantly repressed the growth of pre-established Huh-7 tumors in athymic mouse models accompanying the decreased density of CD34 positive vessels in tumors. In conclusion, our results suggest that antiangiogenic gene therapy using tum-1 gene may be an efficient strategy for the treatment of HCC.
Goto T, Ishikawa H, Matsumoto K, Nishimura D, Kusaba M, Taura N, Shibata H, Miyaaki H, Ichikawa T, Hamasaki K, Nakao K, Maeshima Y, Eguchi K.
First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.