Growth Inhibition of Insulin-Like Growth Factor I Receptor Monoclonal Antibody to Human Colorectal Cancer Cells

Abstract

Aim: Insulin-like growth factors (IGFs) and their receptors play a critical role in the growth and regulation of many type of malignant cells. The purpose of this study was to clarify the expression of Insulin-like growth factor I receptor (IGF-IR) in a human colorectal cancer cell line HT-29 and investigate the effects of 2 IGF-IR monoclonal antibodies (Mab) on the biological behavior of HT-29 cell line. Methods: Immunohistochemistry was used to test the expression of IGF-IR in HT-29 cell line, MTT assay was used to determine the antiproliferation effects of 2 kinds of IGF-IR monoclonal antibody on HT-29 cells. The effects of apoptosis rate and cell cycle of HT-29 cells were estimated by flow cytometry (FCM). Results: IGF-IR was expressed in the membranes of HT-29 cell line; MTT results show that each IGF-IR (α-Subunit)Ab-3 Mab group has remarkable difference (p < 0.01) as compared with control group, each IGF-IRα(1H7)L Mab group has no remarkable difference (p > 0.05) as compared with control group, each IGF-IRα(1H7)L Mab group has light antiproliferation effect on the HT-29 cells. IGF-IR(α-Subunit)Ab-3 has stronger antiproliferation effect on the HT-29 cells and dose-depended growth inhibition effects were observed when concentration is less than 1.5 ug/ml;The 2 kinds of IGF-IR monoclonal antibody can arrest the cell cycle at any phase of HT-29 cells and induce apoptosis. Under the incubating conditions of containing 5 percent fetal bovine serum (FCS) and no FCS, the apoptosis percentage of IGF-IR(α-Subunit)Ab-3 group and IGF-IRα(1H7)L group have obviously increased (p < 0.01). After the number of cells was increased 30 times, the apoptosis percentage of IGF-IR(α-Subunit)Ab-3 group and IGF-IRα(1H7)L group have no remarkable differences as compared with control group (p > 0.05). Conclusions: Blockade of the IGF-IR with IGF-IR Mab inhibiting proliferation, arresting cell cycle and inducing apoptosis of HT-29 cells may represent a valid approach to inhibit tumor growth.

Keywords:

• Insulin-like growth factor-I
• Receptor
• Monoclonal antibody
• Colorectal cancer