title: Phosphorylation of eIF2α suppresses cisplatin-induced A549 cell apoptosis via p38 inhibition.
abstract: 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 2α (eIF2α) suppresses cisplatin-induced A549 cell apoptosis. Cisplatin induced eIF2α phosphorylation through protein kinase RNA. Importantly, phospho-eIF2α inhibited cisplatin-induced A549 cells apoptosis, at least in part, by suppressing the p38 pathway. Moreover, analysis of tissue microarrays information demonstrated that phospho-eIF2α predicted a poor prognosis in patients with NSCLC. Taken together, these results provide a potential mechanism that is used for explaining how eIF2α promotes cisplatin resistance in A549 cells. Therefore, the regulation of eIF2α may improve treatment outcomes of cisplatin-based chemotherapy for patients with NSCLC.
authors.affiliation: 1 Department of Cardio-Thoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine , Shanghai, 200092, P.R. China .
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Run
authors.initials: R
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.forename: Haibo
authors.initials: H
authors.lastname: Xiao
authors.forename: Yin
authors.initials: Y
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Chen
authors.forename: Ju
authors.initials: J
authors.lastname: Mei
authors.forename: Fangbao
authors.initials: F
authors.lastname: Ding
authors.forename: Hong
authors.initials: H
authors.lastname: Zhong
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D011379:Prognosis; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D046888:Tissue Array Analysis; D019892:eIF-2 Kinase / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D002934:Cinnamates; D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D007093:Imidazoles; D011725:Pyridines; C496827:salubrinal; D019892:eIF-2 Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D013890:Thiourea; C093642:SB 203580; D002945:Cisplatin
keywords: A549 cells; apoptosis; cisplatin; eIF2α; p38