α7-Nicotine acetylcholine receptor mediated nicotine induced cell survival and cisplatin resistance in oral cancer

Chia-Chen Hsu; Kuo-Yang Tsai; Yu-Fu Su; Chu-Yen Chien; Ying-Chen Chen; Yu-Chiao Wu; Shyun-Yeu Liu; Yi-Shing Shieh

doi:10.1016/j.archoralbio.2020.104653

α7-Nicotine acetylcholine receptor mediated nicotine induced cell survival and cisplatin resistance in oral cancer

Arch Oral Biol. 2020 Mar:111:104653. doi: 10.1016/j.archoralbio.2020.104653. Epub 2020 Jan 8.

Authors

Chia-Chen Hsu¹, Kuo-Yang Tsai², Yu-Fu Su³, Chu-Yen Chien¹, Ying-Chen Chen⁴, Yu-Chiao Wu⁵, Shyun-Yeu Liu⁶, Yi-Shing Shieh⁷

Affiliations

¹ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan.
² Department of Oral and Maxillofacial Surgery, Changhua Christian Hospital, Changhua, Taiwan; College of Nursing and Health Science, Da-Yeh University, Changhua, Taiwan.
³ Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁴ Molecular and Cell Biology, Taiwan International Graduate Program, Academia Sinica and Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan.
⁵ Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
⁶ Department of Oral and Maxillofacial Surgery, Chi Mei Medical Center, Tainan, Taiwan.
⁷ Department of Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan. Electronic address: ndmcyss@mail.ndmctsgh.edu.tw.

PMID: 31935534
DOI: 10.1016/j.archoralbio.2020.104653

Abstract

Objective: To investigate the effect of nicotine on cell survival and cisplatin resistance in oral cancer and the possible involvement of α7-nicotinic acetylcholine receptors (α7-nAChRs).

Design: The effects of nicotine on cell survival and cisplatin-induced apoptosis were assessed. Knockdown of α7-nAChRs by short hairpin RNA and the specific antagonist methyllycaconitine (MLA) was used to examine the involvement of α7-nAChRs in modulating the effects of nicotine. Apoptosis signal molecules were examined in nicotine- and cisplatin-treated cells.

Results: Nicotine increased the survival of the oral cancer cells YD8 and OEC-M1 in a dose- and time-dependent manner. Nicotine treatment accelerated cell cycle progression in the oral cancer cells, and significantly reduced cisplatin-induced cell apoptosis. In the α7-nAChR-silenced cells, the prosurvival effect of nicotine in the cisplatin-treated cells was attenuated. Co-treatment of cisplatin and nicotine attenuated the effect of cisplatin on Bcl-2 expression. In addition, the effect of nicotine on cell survival under cisplatin treatment was attenuated with the addition of the Bcl-2 inhibitor ABT-737.

Conclusions: Treating oral cancer cells with nicotine increased cell survival and cisplatin resistance, in which α7-nAChRs were involved.

Keywords: Acetylcholine receptors; Apoptosis; Cisplatin resistance; Nicotine.

MeSH terms

Cell Survival*
Cisplatin
Humans
Mouth Neoplasms
Nicotine
alpha7 Nicotinic Acetylcholine Receptor

Substances

alpha7 Nicotinic Acetylcholine Receptor
Nicotine
Cisplatin