Inhibition of hepatocellular carcinoma cell growth by an anti-insulin-like growth factor-I receptor monoclonal antibody

  • Authors:
    • Lu Yue
    • Ying Wang
    • Huamao Wang
    • Huiping Gao
    • Jun Liang
    • Aihua Sui
    • Jinyu Xiang
    • Fang Zhou
    • Congcong Xu
    • Wenwen Zhao
    • Wanhua Liang
    • Ruyong Yao
  • View Affiliations

  • Published online on: August 8, 2012     https://doi.org/10.3892/or.2012.1960
  • Pages: 1453-1460
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Abstract

Hepatocellular carcinoma (HCC) overexpresses insulin-like growth factor-I receptor (IGF-IR), as compared with normal hepatocytes. Since IGF-1R-mediated signaling promotes survival, oncogenic transformation and tumor growth and spread, it represents a potential target for treating HCC. Here, we have generated a murine anti-IGF-1R antibody, 4F2, that recognizes the IGF-IRα subunit and blocks in vitro IGF-I and IGF-II-induced cell proliferation of SMMC-7721 and Bel-7402 HCC cell lines. 4F2 can inhibit IGF-IR autophosphorylation, IRS-1 phosphorylation and the activation of the major downstream signaling molecules AKT and mitogen-activated protein kinase. Additionally, we observed a moderate increase in apoptosis as demonstrated by detection of changes in the expression of the pro-apoptotic and anti-apoptotic proteins Bax and Bcl-2 after 4F2 treatment. Combined treatment with 4F2 and doxorubicin was more effective in reducing cell proliferation and promoting apoptosis than either agent alone. These data support that therapeutic anti-IGF-IR antibodies are potential new agents for treating HCC.
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October 2012
Volume 28 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yue L, Wang Y, Wang H, Gao H, Liang J, Sui A, Xiang J, Zhou F, Xu C, Zhao W, Zhao W, et al: Inhibition of hepatocellular carcinoma cell growth by an anti-insulin-like growth factor-I receptor monoclonal antibody. Oncol Rep 28: 1453-1460, 2012
APA
Yue, L., Wang, Y., Wang, H., Gao, H., Liang, J., Sui, A. ... Yao, R. (2012). Inhibition of hepatocellular carcinoma cell growth by an anti-insulin-like growth factor-I receptor monoclonal antibody. Oncology Reports, 28, 1453-1460. https://doi.org/10.3892/or.2012.1960
MLA
Yue, L., Wang, Y., Wang, H., Gao, H., Liang, J., Sui, A., Xiang, J., Zhou, F., Xu, C., Zhao, W., Liang, W., Yao, R."Inhibition of hepatocellular carcinoma cell growth by an anti-insulin-like growth factor-I receptor monoclonal antibody". Oncology Reports 28.4 (2012): 1453-1460.
Chicago
Yue, L., Wang, Y., Wang, H., Gao, H., Liang, J., Sui, A., Xiang, J., Zhou, F., Xu, C., Zhao, W., Liang, W., Yao, R."Inhibition of hepatocellular carcinoma cell growth by an anti-insulin-like growth factor-I receptor monoclonal antibody". Oncology Reports 28, no. 4 (2012): 1453-1460. https://doi.org/10.3892/or.2012.1960