Induction of G(2)/M Phase Arrest and Apoptosis by Zgdhu-1 in A549 and Rerf-Lc-Ma Lung Cancer Cells

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  • 作者:Shen, X., Wu, Z., Chen, S., Chen, Y., Xia, J., Lv, Y. & Zhou, Y.
  • 期刊:Oncology letters 12, 989-994 (2016)
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Lung cancer is a major public health issue worldwide and is associated with high mortality and poor prognosis. Chemotherapy has the potential to reduce tumor size, increase operability and eradicate micrometastases; therefore, novel chemicals to treat lung cancer are urgently required. In the present study, the effects of N, N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4, 5-tetrazine-1,4-dicarboamide (ZGDHu-1), a novel tetrazine derivative, were investigated in A549 and RERF-LC-MA lung cancer cells, and the underlying molecular mechanism of ZGDHu in treating lung cancer was determined. Following incubation with different concentrations of ZGDHu-1, flow cytometry analysis results indicated that ZGDHu-1 could induce G(2)/mitotic (M) cell cycle arrest and apoptosis in A549 and RERF-LC-MA cells in a dose-dependent manner. Furthermore, western blot analysis demonstrated that the expression levels of G(2)/M regulatory molecules, including cyclin B1, Cdc2 and cell division cycle 25c, decreased following treatment with ZGDHu-1, whilst p53 expression increased. In addition, A549 and RERF-LC-MA cell apoptosis was induced by cell cycle arrest at the G(2)/M phase and through the downregulation of nuclear factor-κB. These results suggest that ZGDHu-1 may induce G(2)/M phase arrest and apoptosis of lung cancer cells, and may serve as a potential therapeutic drug for the treatment of lung cancer.

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