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

  • Authors:
    • Yuwen Xue
    • Hening Ren
    • Wei Xiao
    • Zuoming Chu
    • J. Jack Lee
    • Li Mao
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  • Published online on: September 4, 2012     https://doi.org/10.3892/ijo.2012.1619
  • Pages: 1798-1808
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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).
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November 2012
Volume 41 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Xue Y, Ren H, Xiao W, Chu Z, Lee JJ and Mao L: Antitumor activity of AZ64 via G2/M arrest in non-small cell lung cancer. Int J Oncol 41: 1798-1808, 2012
APA
Xue, Y., Ren, H., Xiao, W., Chu, Z., Lee, J.J., & Mao, L. (2012). Antitumor activity of AZ64 via G2/M arrest in non-small cell lung cancer. International Journal of Oncology, 41, 1798-1808. https://doi.org/10.3892/ijo.2012.1619
MLA
Xue, Y., Ren, H., Xiao, W., Chu, Z., Lee, J. J., Mao, L."Antitumor activity of AZ64 via G2/M arrest in non-small cell lung cancer". International Journal of Oncology 41.5 (2012): 1798-1808.
Chicago
Xue, Y., Ren, H., Xiao, W., Chu, Z., Lee, J. J., Mao, L."Antitumor activity of AZ64 via G2/M arrest in non-small cell lung cancer". International Journal of Oncology 41, no. 5 (2012): 1798-1808. https://doi.org/10.3892/ijo.2012.1619