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Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis.


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Title: Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis.
Authors: Goto, Takashi / Ishikawa, Hiroki / Matsumoto, Kojiro / Nishimura, Daisuke / Kusaba, Mariko / Taura, Naota / Shibata, Hidetaka / Miyaaki, Hisamitsu / Ichikawa, Tatsuki / Hamasaki, Keisuke / Nakao, Kazuhiko / Maeshima, Yohei / Eguchi, Katsumi
Issue Date: Jul-2008
Publisher: Spandidos Publications
Citation: International Journal of Oncology, 33(1), pp.33-40; 2008
Abstract: 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.
Keywords: tum-1 / tumstatin / hepatocellular carcinoma / angiogenesis
URI: http://hdl.handle.net/10069/22339
ISSN: 10196439
PubMed ID: 18575748
Relational Links: http://hdl.handle.net/10069/26711
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/22339

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