Effect of anti-EGFR monoclonal antibody on chemosensitivity of human colon cancer cells and the mechanism.
- Author:
Meng-ran CAO
1
;
Xiao-yan LI
;
Da-yong ZHENG
;
Lin YANG
;
Cheng-wei LV
;
Rong-cheng LUO
Author Information
- Publication Type:Journal Article
- MeSH: Antibodies, Monoclonal, Humanized; therapeutic use; Antineoplastic Combined Chemotherapy Protocols; therapeutic use; Cell Line, Tumor; Cetuximab; Colonic Neoplasms; drug therapy; metabolism; Humans; Oncogene Protein v-akt; metabolism; Receptor, Epidermal Growth Factor; immunology; Signal Transduction
- From: Journal of Southern Medical University 2010;30(8):1817-1823
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of anti-EGFR monoclonal antibody on the chemosensitivity of human colon cancer cells and explore the possible molecular mechanism.
METHODSThe inhibitory effect of irinotecan (CPT-11), oxaliplatin (L-OHP) and fluorouracil (5-Fu), used alone or in combination with anti-EGFR monoclonal antibody, on the proliferation of LoVo cells in vitro was assessed by MTT assay. The expressions of PI3K and Akt protein in the treated cells were examined by Western blotting, and their mRNA expressions were detected by RT-PCR.
RESULTSBoth h-R3 and C-225 treatments significantly increased the chemosensitivity of LoVo cells to irinotecan and oxaliplatin. 5-Fu and h-R3 coadministered showed a synergistic effect on the cells, but 5-Fu and C-225 had an antagonistic action. Treatment with C-225 or h-R3 resulted in lowered expressions of PI3K and Akt in LoVo cells.
CONCLUSIONAnti-EGFR monoclonal antibody can increase the chemosensitivity of human colon cancer cells to most chemotherapeutic drugs, and such effect might be attributed to the blocking of PI3K/Akt signaling pathway by these antibodies.