Novel irreversible EGFR tyrosine kinase inhibitor 324674 sensitizes human colon carcinoma HT29 and SW480 cells to apoptosis by blocking the EGFR pathway.

摘要: Abstract Background Epidermal growth factor receptor (EGFR) is widely expressed in multiple solid tumors including colorectal cancer by promoting cell and proliferation. Therefore, the inhibition of EGFR activity may establish a clinical strategy therapy. Methods In this study, using human colon adenocarcinoma HT29 SW480 cells as research models, we compared efficacy four inhibitors EGFR-mediated pathways, novel irreversible inhibitor 324674, conventional reversible AG1478, dual EGFR/HER2 GW583340 pan-EGFR/ErbB2/ErbB4 inhibitor. Cell proliferation was assessed MTT analysis, apoptosis evaluated Annexin-V binding assay. its downstream signaling effectors were examined western blotting analysis. Results Among inhibitors, 324674 more potent at inhibiting able to efficiently induce lower concentrations. Western analysis revealed that failed suppress activation well mitogen-activated protein kinase (MAPK) PI3K/AKT/mTOR (AKT) pathways. contrast, inhibited AKT pathway dose-dependent manner. Conclusion Our studies indicated have therapeutic application