Antitumor activity of AZ64 via G2/M arrest in non-small cell lung cancer

Int J Oncol. 2012 Nov;41(5):1798-808. doi: 10.3892/ijo.2012.1619. Epub 2012 Sep 4.


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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chromosomes, Human / drug effects
  • Chromosomes, Human / metabolism
  • Dose-Response Relationship, Drug
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • Microtubules / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / metabolism
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Protein Kinases
  • tropomyosin kinase