Inhibition of hepatocellular carcinoma cell growth by an anti-insulin-like             growth factor-I receptor monoclonal antibody.
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.
Department of Oncology, Affiliated Hospital of Qingdao University, Medical College, Qingdao, PR China.
Lu
L
Yue
Ying
Y
Wang
Huamao
H
Wang
Huiping
H
Gao
Jun
J
Liang
Aihua
A
Sui
Jinyu
J
Xiang
Fang
F
Zhou
Congcong
C
Xu
Wenwen
W
Zhao
Wanhua
W
Liang
Ruyong
R
Yao
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000911:Antibodies, Monoclonal; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004317:Doxorubicin; D017526:Receptor, IGF Type 1