Knockdown of TRAF1 in NSCIC Contributes Gefitinib Sensitivity by Promoting G2/M Cell Cycle Arrest

Abstract Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) achieves remarkable success in the treatment of patients with advanced non-small cell lung cancer (NSCLC) bearing activating EGFR mutations. However, EGFR-TKI resistance is still a obstacles in the clinical practice. TRAF1 as a member of TRAF family participates NSCLC progression. In our previous research found that TRAF1 played an important role in the progression of NSCLC.Methods: In vivo and vitro, quantitative PCR (qPCR) and western blot (WB) were carried out to check the expression of TRAF1 in gefitinib-sensitive and -resistant NSCLC samples. The cell counting kit-8 (CCK8) and flow cytometry were used to measure cell proliferation, apoptosis and cycle arrest.Results: Here we showed that TRAF1 over-expression is associated with clinical resistance to EGFR TKI. TRAF1 was significantly up-regulated in gefitinib-resistant cells. Knockdown of TRAF1 increased the sensitivity of gefitinib-resistant cell. Knockdown of TRAF1 induced cell apoptosis and cell cycle arrest. Conclusions: Therefore, our results highlight the function of TRAF1 in the EGFT-TKI resistance.