title: Antitumor activity of AZ64 via G2/M arrest in non-small cell lung cancer.
abstract: AZ64 is a novel antitumor agent designed as a tropomyosin-related kinase             (Trk) inhibitor; however, its effect on lung cancer and its mechanism of action             remain unclear. This study aimed to elucidate the antitumor activity of AZ64 and             its mechanism of action against non-small cell lung cancer (NSCLC). Our results             demonstrate that AZ64 has a potent anti-proliferative effect on NSCLC cells and             acts in a dose- and time-dependent manner. We also demonstrate that AZ64 suppresses             the anchorage-independent growth and invasion of NSCLC cells. In vivo experiments             demonstrated that AZ64 significantly reduced the tumor growth of NSCLC xenografts             in nude mice and was well-tolerated. Mechanistic experiments revealed that AZ64             induced the G2/M arrest of NSCLC cells by the accumulation of phospho-cdc2 (Tyr15)             at the G2/M transition, following the downregulation of Cdc25C expression. Collectively,             our data demonstrate that AZ64 is a potential antitumor drug that may be used             for the treatment of NSCLC, which functions by targeting the G2/M transition via             the inhibition of the dephosphorylation of phospho-cdc2 (Tyr15).
authors.affiliation: Department of Respiratory Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Xue
authors.forename: Hening
authors.initials: H
authors.lastname: Ren
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Zuoming
authors.initials: Z
authors.lastname: Chu
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Li
authors.initials: L
authors.lastname: Mao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002877:Chromosomes, Human / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008870:Microtubules / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C041311:tropomyosin kinase