Phosphorylation of eIF2α Suppresses Cisplatin-Induced A549 Cell Apoptosis via p38 Inhibition

Cisplatin-based chemotherapy is considered a golden standard for treatment of advanced non-small cell lung cancer (NSCLC). However, drug resistance is one of the major problems in NSCLC chemotherapy. The mechanisms and related biological pathways that contribute to chemoresistance are relatively poorly understood. Here, we demonstrated that the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2 alpha) suppresses cisplatin-induced A549 cell apoptosis. Cisplatin induced eIF2 alpha phosphorylation through protein kinase RNA. Importantly, phospho-eIF2 alpha inhibited cisplatin-induced A549 cells apoptosis, at least in part, by suppressing the p38 pathway. Moreover, analysis of tissue microarrays information demonstrated that phospho-eIF2 alpha predicted a poor prognosis in patients with NSCLC. Taken together, these results provide a potential mechanism that is used for explaining how eIF2 alpha promotes cisplatin resistance in A549 cells. Therefore, the regulation of eIF2 alpha may improve treatment outcomes of cisplatin-based chemotherapy for patients with NSCLC.