TY - JOUR AB - 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. AD - Department of Oncology, Affiliated Hospital of Qingdao University, Medical College, Qingdao, P.R. China Shanghai Xuhui Central Hospital, Shanghai, P.R. China State Key Laboratory of Oncogenes and Related Genes, Renji Hospital, Medical School of Shanghai JiaoTong University, Shanghai, P.R. China Central Laboratory, Affiliated Hospital of Qingdao University, Medical College, Qingdao, P.R. China AU - Yue,Lu AU - Wang,Ying AU - Wang,Huamao AU - Gao,Huiping AU - Liang,Jun AU - Sui,Aihua AU - Xiang,Jinyu AU - Zhou,Fang AU - Xu,Congcong AU - Zhao,Wenwen AU - Liang,Wanhua AU - Yao,Ruyong DA - 2012/10/01 DO - 10.3892/or.2012.1960 EP - 1460 IS - 4 JO - Oncol Rep KW - IGF-IR 4F2 HCC doxorubicin apoptosis PY - 2012 SN - 1021-335X 1791-2431 SP - 1453 ST - Inhibition of hepatocellular carcinoma cell growth by an anti-insulin-like growth factor-I receptor monoclonal antibody T2 - Oncology Reports TI - Inhibition of hepatocellular carcinoma cell growth by an anti-insulin-like growth factor-I receptor monoclonal antibody UR - https://doi.org/10.3892/or.2012.1960 VL - 28 ER -