α7 nicotinic acetylcholine receptor is a potential novel therapeutic target for
PUBLISHED: 2015-11-30  362 total views, 1 today

Kailin Xing1, Aiqun Hu2, Xianghua Wu1 

1Medical Oncology, Fudan University Shanghai Cancer Center, 2Renji Hospital, Shanghai Cancer Institute

 

Objective:Nicotine and its associated nicotinic acetylcholine receptors (nAChRs) are believed to be involved in the progression of some solid carcinomas by regulating cell proliferation, apoptosis, tumor invasion and angiogenesis. But whether nAChR contributes to the development of hepatocellular carcinoma (HCC) is still unknown. The aim of this study was to investigate the potential roles of nAChR in regulating cell proliferation and tumor invasion of HCC. Method: RT-PCR and Immunofluorescence cytochemistry were used to assess nAChR expression in HCC cell lines and tissue samples. The effects of nicotine and nAChR antagonists on HCC cell proliferation and apoptosis were assessed. nAChR mediated migration and invasion were evaluated by transwell migration assay and wound-healing assay. Result:α2, α5, α7, α9, β2 and β4 nAChR subunits were expressed in most HCC cell lines and tissue samples. Results showed that α7 nAChR mediated the proliferation, migration and invasion activity of nicotine in HCC cells. In contrast, inhibition of nAChR by siRNA or nAChR antagonists greatly inhibited those activities. Apoptosis analysis demonstrated that nicotine inhibited apoptosis of HCC cells. We also found nicotine could upregulate α7 subunit expression which facilitates HCC cell proliferation and invasion. Conclusion:α7 nAChR plays a key role in regulating HCC cell proliferation and invasion in vitro. Our results suggest that α7 nAChR might be a valuable therapeutic target for HCC.

 

Key Words: α7  nicotinic acetylcholine receptor Hepatocellular


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