Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability
Autor: | Takashi Nishioka, Mariyannis A, Dai W, Luo Ly, Chen C, Shen L, He H |
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Rok vydání: | 2013 |
Předmět: |
Cancer Research
Nicotine Keap1 Lung Neoplasms cisplatin Antineoplastic Agents Apoptosis Biology 03 medical and health sciences Mice 0302 clinical medicine medicine Tumor Cells Cultured Animals Humans Bcl-2 Cytotoxicity Protein kinase B Molecular Diagnostics 030304 developmental biology Cisplatin 0303 health sciences Cell growth Protein Stability Akt Ubiquitination chemoresistance KEAP1 3. Good health Up-Regulation Oncology Proto-Oncogene Proteins c-bcl-2 Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer cell Immunology Cancer research Protein Processing Post-Translational medicine.drug |
Zdroj: | British Journal of Cancer |
ISSN: | 1532-1827 |
Popis: | 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. |
Databáze: | OpenAIRE |
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