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

  • Authors:
    • Takashi Goto
    • Hiroki Ishikawa
    • Kojiro Matsumoto
    • Daisuke Nishimura
    • Mariko Kusaba
    • Naota Taura
    • Hidetaka Shibata
    • Hisamitsu Miyaaki
    • Tatsuki Ichikawa
    • Keisuke Hamasaki
    • Kazuhiko Nakao
    • Yohei Maeshima
    • Katsumi Eguchi
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.33
  • Pages: 33-40
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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.

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July 2008
Volume 33 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Goto T, Ishikawa H, Matsumoto K, Nishimura D, Kusaba M, Taura N, Shibata H, Miyaaki H, Ichikawa T, Hamasaki K, Hamasaki K, et al: Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis. Int J Oncol 33: 33-40, 2008.
APA
Goto, T., Ishikawa, H., Matsumoto, K., Nishimura, D., Kusaba, M., Taura, N. ... Eguchi, K. (2008). Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis. International Journal of Oncology, 33, 33-40. https://doi.org/10.3892/ijo.33.1.33
MLA
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."Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis". International Journal of Oncology 33.1 (2008): 33-40.
Chicago
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."Tum-1, a tumstatin fragment, gene delivery into hepatocellular carcinoma suppresses tumor growth through inhibiting angiogenesis". International Journal of Oncology 33, no. 1 (2008): 33-40. https://doi.org/10.3892/ijo.33.1.33