title: Effect and mechanism of Src tyrosine kinase inhibitor sunitinib on the drug-resistance reversal of human A549/DDP cisplatin-resistant lung cancer cell line.
abstract: The development of tumor cell drug resistance is the primary reason for treatment failure in lung cancer chemotherapy. Therefore, overcoming multidrug resistance is currently an urgent issue to be addressed in lung cancer treatment. Sunitinib is a tyrosine kinase inhibitor with confirmed inhibitory effects on tumor growth and metastasis; however, the effects of sunitinib and mechanisms of action in lung cancer multidrug resistance are yet to be determined. The present study was designed to examine the effects of sunitinib and the mechanisms underlying lung cancer multidrug resistance. It was observed that sunitinib was able to improve the sensitivity of A549/DDP lung cancer cells to cisplatin, enhance tumor apoptosis, arrest the cell cycle in G0/G1 phase, upregulate intracellular Rh-123 content, downregulate the expression of P-glycoprotein, multidrug resistance protein 1, multidrug resistance-associated protein 1, lung resistance protein, glutathione-S-transferase, ERCC1, survivin and Bcl-2 in tumor cells, phosphorylation of AKT and extracellular signal-regulated kinase (ERK), glutathione activity, and transcriptional activity of nuclear factor-κB, Twist, Snail and AP-1. The results demonstrated that sunitinib was able to reverse the multidrug resistance of A549/DDP lung cancer cells, which was possibly associated with the downregulation of multidrug resistance-associated gene expression and the inhibition of AKT and ERK phosphorylation.
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, Henan 471003, P.R. China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000633:toxicity*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011758:Pyrroles / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D000077210:Sunitinib; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D048049:Extracellular Signal-Regulated MAP Kinases; D007211:Indoles; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D051057:Proto-Oncogene Proteins c-akt; D011758:Pyrroles; D000077210:Sunitinib; D019061:src-Family Kinases