Synergistic interaction between MEK inhibitor and gefitinib in EGFR‑TKI‑resistant human lung cancer cells

摘要: With the increasing use of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) in patients with advanced non-small cell lung cancer (NSCLC), acquired resistance has become a major clinical problem. A combination different signaling pathway inhibitors is promising strategy to overcome this. In present study, mitogen-activated protein 1/2 inhibitor, AZD6244, was used gefitinib investigate efficacy this treatment NSCLC lines, particularly gefitinib-resistant cells. The EGFR-TKI-sensitive PC-9 (mutant EGFR/wild-type K-Ras) and EGFR-TKI-resistant A549 (wild-type EGFR/mutant human lines were treated AZD6244 alone, alone or two drugs, effects evaluated using proliferation assays, alterations pathways analyzed by western blotting. It found that inhibitory effect greater than Treatment cells reduced expression level activated form Akt, drugs showed stronger inhibition phosphorylated-Akt phosphorylated-extracellular signal-regulated kinases. data exhibited dose-dependent synergism Thus, preclinical rationale exists for enhance NSCLC.