Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability

T. Nishioka, L. Y. Luo, L. Shen, H. He, A. Mariyannis, W. Dai, C. Chen

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Background:Nicotine is able to activate mitogenic signalling pathways, which promote cell growth or survival as well as increase chemoresistance of cancer cells. However, the underlying mechanisms are not fully understood.Methods:In this study, we used immunoblotting and immunoprecipitation methods to test the ubiquitination and degradation of Bcl-2 affected by nicotine in lung cancer cells. Apoptotic assay was also used to measure the antagonising effect of nicotine on cisplatin-mediated cytotoxicity.Results:We demonstrated that the addition of nicotine greatly attenuated Bcl-2 ubiquitination and degradation, which further desensitised lung cancer cells to cisplatin-induced cytotoxicity. In this process, Bcl-2 was persistently phosphorylated in the cells cotreated with nicotine and cisplatin. Furthermore, Akt was proven to be responsible for sustained activation of Bcl-2 by nicotine, which further antagonised cisplatin-mediated apoptotic signalling.Conclusions: Our study suggested that nicotine activates its downstream signalling to interfere with the ubiquitination process and prevent Bcl-2 from being degraded in lung cancer cells, resulting in the increase of chemoresistance.

Original languageEnglish
Pages (from-to)1785-1792
Number of pages8
JournalBritish Journal of Cancer
Issue number7
Publication statusPublished - 2014 Apr 1


  • Akt
  • Bcl-2
  • chemoresistance
  • cisplatin
  • Keap1
  • nicotine
  • ubiquitination


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