Growth inhibition of insulin-like growth factor I receptor monoclonal antibody to human colorectal cancer cells.
OBJECTIVE
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.
Zhang
Youcheng
Y
Department of General Surgery, Second Hospital of Lanzhou University, Lanzhou, Gansu Province, China.
Zhang
Yawu
Y
D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005434:Flow Cytometry; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000187:drug effects*
D000911:Antibodies, Monoclonal; D017526:Receptor, IGF Type 1