Abstract | BACKGROUND: METHODS: Human CRC cells were treated in vitro with anti-IGF-IR monoclonal antibody (MoAB) with and without oxaliplatin to assess cytotoxicity. The effect of anti-IGF-IR MoAB on IGF-I-induced vascular endothelial growth factor ( VEGF) production in human CRC cells was assessed by Northern blot and ELISA. We injected human CRC cells intrahepatically in nude mice, and then administered anti-IGF-IR MoAB with and without oxaliplatin. We delayed treatment in one group until large hepatic tumors were present. We assessed tumors for apoptosis, proliferation, and angiogenesis. RESULTS: Anti-IGF-IR MoAB and oxaliplatin inhibited CRC cell growth in vitro and combination treatment was even more effective. IGF-I stimulation of CRC cells resulted in significant upregulation of VEGF and this was completely inhibited by pretreatment with anti-IGF-IR MoAB. Anti-IGF-IR MoAB significantly inhibited hepatic growth of tumors in mice. Anti-IGF-IR MoAB plus oxaliplatin led to a significantly greater inhibition of tumor growth. Anti-IGF-IR MoAB plus oxaliplatin was just as effective at inhibiting growth of larger, more advanced liver tumors. Anti-IGF-IR MoAB, alone and in combination with oxaliplatin, led to a significant increase in tumor cell apoptosis, and a significant inhibition of tumor cell proliferation and angiogenesis. CONCLUSIONS: These findings suggest that IGF-IR is a potential target for therapy in patients with advanced CRC.
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Authors | Todd W Bauer, Fan Fan, Wenbiao Liu, Ernest R Camp, Anthony Yang, Ray J Somcio, Corazon D Bucana, Rajeeva Singh, Lee M Ellis |
Journal | Annals of surgical oncology
(Ann Surg Oncol)
Vol. 14
Issue 10
Pg. 2838-46
(Oct 2007)
ISSN: 1068-9265 [Print] United States |
PMID | 17653802
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- Organoplatinum Compounds
- Vascular Endothelial Growth Factor A
- Oxaliplatin
- Receptor, IGF Type 1
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Topics |
- Animals
- Antibodies, Monoclonal
(pharmacology)
- Antineoplastic Agents
(pharmacology)
- Apoptosis
(drug effects)
- Blotting, Northern
- Cell Division
(drug effects)
- Cell Survival
(drug effects)
- Colorectal Neoplasms
(pathology)
- Enzyme-Linked Immunosorbent Assay
- HT29 Cells
(drug effects, pathology, transplantation)
- Humans
- In Situ Nick-End Labeling
- In Vitro Techniques
- Liver Neoplasms, Experimental
(pathology, secondary)
- Male
- Mice
- Mice, Nude
- Neoplasm Transplantation
- Neovascularization, Pathologic
(pathology)
- Organoplatinum Compounds
(pharmacology)
- Oxaliplatin
- Receptor, IGF Type 1
(antagonists & inhibitors)
- Vascular Endothelial Growth Factor A
(metabolism)
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