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Nicotine inhibits cisplatin-induced apoptosis in NCI-H446 cells

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Abstract

Nicotine is not only a major component in tobacco but is also a survival agonist that inhibits apoptosis induced by certain agents including chemotherapeutic drugs. Here, we first showed that nicotine inhibits cisplatin-induced apoptosis in NCI-H446 cells. An MTT assay, Annexin V-FITC staining, RT-PCR, and Western blot were applied to identify the viability of cells, stages of apoptosis, mRNA and signaling proteins expression, respectively. First, we observed that nicotine induced no significant apoptosis when used alone and promoted cell proliferation at a low concentration or for a short time, but the opposite was observed at a high concentration or for a long time. In addition, an increase in XIAP and Survivin mRNA or protein was observed. Next, when combined with cisplatin, growth inhibition rates were concentration dependent, decreased to the lowest level at first, but later climbed to the highest point. Furthermore, nicotine inhibited apoptosis induced by cisplatin and caused a concentration-dependent increase in both XIAP and Survivin mRNA or protein. Moreover, the apoptotic effect of the combination group was obviously higher than that of nicotine used alone at the same nicotine concentration and lower than that of cisplatin used alone at the same cisplatin concentration. These studies suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutics.

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Acknowledgments

This work was supported by a grant from the Science and Technology Project of Zhoushan, Zhejiang Province, China (No. 081058) and Program for New Century Excellent Talents in University of China (2007).

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Authors and Affiliations

  1. Joint Laboratory of Immunogenomics, Zhoushan Hospital-Beijing Institute of Genomics Chinese Academy of Sciences, 238 Renming North Road, 316004, Dinghai, Zhejiang, China

    Fang Zeng, Yong Kui Zhang, Ye Kai Wang, Shi Quan Zhou, Li Na Ma, Ji Hang Zhou, Yan Yan Huang, Wang Yu Zhu & Xiao Guang Liu

  2. Department of Infectious Diseases, Zhoushan Hospital, 316004, Zhejiang, China

    Yun Cheng Li

  3. Department of Experimental Center, Hubei University of Traditional Chinese Medicine, 430065, Wuhan, China

    Gang Chen

  4. Department of Cardiothoracic Surgery, Zhoushan Hospital, 316004, Zhejiang, China

    Yong Kui Zhang

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  1. Fang Zeng
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  2. Yun Cheng Li
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  3. Gang Chen
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  9. Yan Yan Huang
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  10. Wang Yu Zhu
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  11. Xiao Guang Liu
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Corresponding author

Correspondence to Xiao Guang Liu.

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F. Zeng and Y. Li contributed equally.

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Zeng, F., Li, Y.C., Chen, G. et al. Nicotine inhibits cisplatin-induced apoptosis in NCI-H446 cells. Med Oncol 29, 364–373 (2012). https://doi.org/10.1007/s12032-010-9792-9

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  • DOI: https://doi.org/10.1007/s12032-010-9792-9

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