Abstract
Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for nearly 85% of all lung cancer cases. In patients with NSCLC whose tumors harbor epidermal growth factor receptor (EGFR) activating mutation, gefitinib is the first-line treatment. However, most patients ultimately obtain drug resistance after 12–18 months treatment. Hence, it is urgent need to investigate the drug resistant mechanism and biomarker. In this study, we used a pair of lung adenocarcinoma cell lines, PC9, and the gefitinib resistant PC9/Gef as a model system to examine resistant mechanism and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI-TOF/TOF MS) to examine the global protein expression changes between PC9 and gefitinib resistant PC9/Gef. A proteomic study revealed that resistant properties altered the expression of 47 proteins in PC9/Gef cells comparing to PC9 cells. Many potential proteins have been validated by western blotting. Further studies have used RNA interference, cell viability analysis, and analysis of apoptosis against progesterone receptor membrane component 1 (mPR) and Pericentrin (PCNT) proteins, to monitor and evaluate their potency and mechanism in resistance. The proteomic approach allowed us to identify numerous proteins, including PCNT, involved in drug resistance mechanism. Our results provide useful diagnostic markers and therapeutic candidates for the treatment of gefitinib-resistant lung adenocarcinoma.