ABSTRACT
OBJECTIVE: To investigate the effect of anti-EGFR monoclonal antibody on the chemosensitivity of human colon cancer cells and explore the possible molecular mechanism. METHODS: The 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. RESULTS: Both 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. CONCLUSION: Anti-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.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Cell Line, Tumor , Cetuximab , Colonic Neoplasms/metabolism , ErbB Receptors/immunology , Humans , Oncogene Protein v-akt/metabolism , Signal TransductionABSTRACT
AIM: To investigate the reversion of multidrug resistance of drug-resistant hepatocellular carcinoma (HCC) cell line BEL-7402/FU by sorafenib and the possible mechanisms. METHODS: Flow cytometry was applied to detect the expression of rhodamine 123 (Rho123), immunohistochemistry was applied to observe the expression of P-glycoprotein (P-gp) on the cell membrane, the fluorescence quantitative PCR assay was applied to determine the changes of the multidrug-resistant gene mdr1 mRNA level and the Western blot assay was applied to test the changes of the expression level of the mdr1 gene product P-gp. RESULTS: After 4 micromol/L treatment by sorafenib, Rho123 accumulation was increased by BEL-7402/FU and exocytosis was slowed down, which evidently reduced the expression of cell surface P-gp; the mdr1 mRNA level was reduced by 35.4% compared to its level prior to drug administration; the expression level of the mdr1 gene product P-gp was significantly suppressed, 14.3% fewer than that of BEL-7402/FU cells. CONCLUSION: Sorafenib can inhibit the expression of the mdr1 gene product P-gp and increase the intracellular concentration of chemotherapeutic drugs, so as to reverse the multidrug resistance of HCC cells.
Subject(s)
Benzenesulfonates/pharmacology , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Pyridines/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Antineoplastic Agents/pharmacology , Blotting, Western , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Membrane/metabolism , Drug Resistance, Multiple/genetics , Drug Resistance, Neoplasm/genetics , Exocytosis/drug effects , Flow Cytometry , Humans , Immunohistochemistry , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Niacinamide/analogs & derivatives , Phenylurea Compounds , Reverse Transcriptase Polymerase Chain Reaction , Rhodamine 123/metabolism , SorafenibABSTRACT
OBJECTIVE: To investigate the clinical significance of vascular endothelial growth factor (VEGF) levels in serums of colorectal cancer patients at stage IV. METHODS: Using enzyme linked immunosorbent assay (ELISA) to detect the VEGF levels in serums of 45 colorectal cancer patients at stage IV, and 20 healthy served as normal control. RESULTS: The mean concentration of VEGF in 45 colorectal cancer patients at the 7 day after operation were significantly lower than that before operation (P<0.01). The mean concentration of VEGF in the patients who benefit from bevacizumab showed no statistical difference from the levels of who did not benefit (P=0.554). CONCLUSION: The VEGF levels in colorectal patients at stage IV are lowed as the load of tumor decrease. The circulating levels of VEGF seem not predict the response to bevacizumab in colorectal cancer patients at stage IV.
