Open AccessAntitumor activity of AZ64 via G2/M arrest in non-small cell lung cancer
Author(s) -
Yingwei Xue,
Hening Ren,
Xiao Wu,
Zuoming Chu,
John Lee,
Mao Li
Publication year - 2012
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2012.1619
Subject(s) - cyclin dependent kinase 1 , cancer research , lung cancer , biology , oncogene , cell cycle , cancer , downregulation and upregulation , mechanism of action , trk receptor , in vivo , kinase , cell growth , pharmacology , medicine , in vitro , microbiology and biotechnology , biochemistry , receptor , genetics , gene , neurotrophin
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).