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).
Original language | English (US) |
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Pages (from-to) | 1798-1808 |
Number of pages | 11 |
Journal | International journal of oncology |
Volume | 41 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2012 |
Keywords
- AZ64
- Cdc25C
- G2/M arrest
- Non-small cell lung cancer
- Phospho-Cdc2 (Tyr15)
ASJC Scopus subject areas
- Oncology
- Cancer Research
MD Anderson CCSG core facilities
- Biostatistics Resource Group