Growth inhibition of insulin-like growth factor I receptor monoclonal antibody to human colorectal cancer cells

Cancer Invest. 2008 Apr-May;26(3):230-6. doi: 10.1080/07357900701508975.

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 (alpha-Subunit)Ab-3 Mab group has remarkable difference (p < 0.01) as compared with control group, each IGF-IRalpha(1H7)L Mab group has no remarkable difference (p > 0.05) as compared with control group, each IGF-IRalpha(1H7)L Mab group has light antiproliferation effect on the HT-29 cells. IGF-IR(alpha-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(alpha-Subunit)Ab-3 group and IGF-IRalpha(1H7)L group have obviously increased (p < 0.01). After the number of cells was increased 30 times, the apoptosis percentage of IGF-IR(alpha-Subunit)Ab-3 group and IGF-IRalpha(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Colorectal Neoplasms / metabolism*
  • Flow Cytometry
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / biosynthesis*
  • Receptor, IGF Type 1 / drug effects*

Substances

  • Antibodies, Monoclonal
  • Receptor, IGF Type 1