title: Stimulatory effects of sorafenib on human non‑small cell lung cancer cells in vitro by regulating MAPK/ERK activation.
abstract: Sorafenib is an inhibitor of a number of intracellular signaling kinases with antiproliferative, anti‑angiogenic and pro‑apoptotic effects in tumor cells. Sorafenib has been used in the therapy of advanced renal cell carcinoma. In the present study, using two human non‑small cell lung cancer (NSCLC)cell lines, A549 and NCI‑H1975, the effects of sorafenib on proliferation, apoptosis and intracellular signaling were systematically characterized. The results revealed that at a low concentration (5 µM) and early time point (6 h), sorafenib is capable of significantly stimulating proliferation of A549 cells, but not NCI‑H1975 cells. In addition, the comparison of the two cell lines revealed different cell cycle redistribution and apoptotic susceptibility to sorafenib at this concentration and time point. Western blot analysis revealed that sorafenib upregulated the expression of cyclin D1 and cyclin‑dependent kinase 2 and downregulated the expression of BAX at this specific point. Furthermore, sorafenib was confirmed to regulate the expression of cyclin D1 and apoptosis‑associated proteins through the regulation of extracellular signal‑regulated kinase 1/2 phosphorylation in A549 cells. These findings suggest that, although sorafenib has the potential for use in the treatment of renal cell carcinoma, this compound may also activate NSCLC cells at a specific time point.
authors.affiliation: Department of Thoracic Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu 215300, P.R. China.
authors.forename: Ya-Nian
authors.initials: YN
authors.lastname: Zhang
authors.forename: Xiao-Yang
authors.initials: XY
authors.lastname: Wu
authors.forename: Ning
authors.initials: N
authors.lastname: Zhong
authors.forename: Jun
authors.initials: J
authors.lastname: Deng
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.forename: Chong-Jun
authors.initials: CJ
authors.lastname: Zhong
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002070:Butadienes / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D000077157:Sorafenib; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002070:Butadienes; D009570:Nitriles; D010671:Phenylurea Compounds; C113580:U 0126; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases