TIP30 inhibits growth of HCC cell lines and inhibits HCC xenografts in mice in combination with 5-FU

Authors

  • Jian Zhao,

    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
    2. Immunology Division, Shanghai Center for Cell Engineering and Antibody and E-Institute, Shanghai, China
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    • Jian Zhao and Xia Zhang contributed equally to this work.

  • Xia Zhang,

    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
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    • Jian Zhao and Xia Zhang contributed equally to this work.

  • Mei Shi,

    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
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  • Hao Xu,

    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
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  • Jun Jin,

    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
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  • Haidong Ni,

    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
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  • Silei Yang,

    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
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  • Jianxin Dai,

    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
    2. Immunology Division, Shanghai Center for Cell Engineering and Antibody and E-Institute, Shanghai, China
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  • Mengchao Wu,

    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
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  • Yajun Guo

    Corresponding author
    1. International Joint Cancer Institute & Eastern Hospital of Hepatobiliary Surgery, Second Military Medical University, Shanghai, China
    2. Immunology Division, Shanghai Center for Cell Engineering and Antibody and E-Institute, Shanghai, China
    • International Joint Cancer Institute, Second Military Medical University, 800 Xiang Yin Road, New Building 10-11th Floor, Shanghai 200433, People's Republic of China
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    • fax: (86) 21-25074349


  • Potential conflict of interest: Nothing to report.

Abstract

Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The specific cellular gene alterations responsible for hepatocarcinogenesis are not well known. Previous works showed that loss of TIP30, also called CC3, a putative tumor suppressor, increased the incidence of hepatocellular carcinoma in mice, and some clinical samples of human HCC tissues had aberrant expression of TIP30. Here, we report that the introduction of TIP30 by an adenovirus vector into HCC cell lines that had decreased expressions of TIP30 inhibited cell proliferation, decreased anchorage-dependent growth, suppressed invasion through the extracellular matrix, and inhibited tumorigenesis in nude mice. Moreover, exogenous expression of Tip30 sensitized HCC cells to cytotoxic drugs and to apoptosis induced by tumor necrosis factor–related ligands in vitro. Ectopic expression of TIP30 in HCC cells enhanced p53 expression and decreased Bcl-2/Bcl-xL expression. Treatment of nude mice bearing subcutaneously established HCC tumors with a combination of an adenovirus expressing TIP30 and the cytotoxic drug 5-fluorouracil completely suppressed tumor growth and prolonged survival. In conclusion, TIP30 may play an important role in the suppression of hepatocarcinogenesis by acting as a tumor suppressor. Overexpression of TIP30 might be a promising candidate as a treatment for HCC that would increase sensitivity to chemotherapeutic drugs. (HEPATOLOGY 2006;44:205–215.)

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