Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis
| Autor: | Hiroki Ishikawa, Katsumi Eguchi, Takashi Goto, Tatsuki Ichikawa, Daisuke Nishimura, Mariko Kusaba, Kazuhiko Nakao, Hidetaka Shibata, Yohei Maeshima, Naota Taura, Keisuke Hamasaki, Hisamitsu Miyaaki, Kojiro Matsumoto |
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| Rok vydání: | 2008 |
| Předmět: |
Collagen Type IV
Male Vascular Endothelial Growth Factor A tum-1 Cancer Research medicine.medical_specialty Carcinoma Hepatocellular Tumstatin Angiogenesis Athymic mouse Biology Gene delivery Autoantigens Mice Phosphatidylinositol 3-Kinases angiogenesis chemistry.chemical_compound Cell Line Tumor Internal medicine medicine Animals Humans Phosphorylation Cell Proliferation Phosphoinositide-3 Kinase Inhibitors Mice Inbred BALB C Neovascularization Pathologic Oncogene Liver Neoplasms Endothelial Cells tumstatin Genetic Therapy hepatocellular carcinoma Transfection Peptide Fragments digestive system diseases Vascular endothelial growth factor Vascular endothelial growth factor A Endocrinology Oncology chemistry Cancer research Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | International Journal of Oncology. |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.33.1.33 |
| Popis: | 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. International Journal of Oncology, 33(1), pp.33-40; 2008 |
| Databáze: | OpenAIRE |
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