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

AZ64 is a novel antitumor agent designed as a tropomyosin-related kinase(Trk) inhibitor; however, its effect on lung cancer and its mechanism of actionremain unclear. This study aimed to elucidate the antitumor activity of AZ64 andits mechanism of action against non-small cell lung cancer (NSCLC). Our resultsdemonstrate that AZ64 has a potent anti-proliferative effect on NSCLC cells andacts in a dose- and time-dependent manner. We also demonstrate that AZ64 suppressesthe anchorage-independent growth and invasion of NSCLC cells. In vivo experimentsdemonstrated that AZ64 significantly reduced the tumor growth of NSCLC xenograftsin nude mice and was well-tolerated. Mechanistic experiments revealed that AZ64induced 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 usedfor the treatment of NSCLC, which functions by targeting the G2/M transition viathe inhibition of the dephosphorylation of phospho-cdc2 (Tyr15).