Shin Nieh1,2, Shu-Wen Jao3, Chin-Yuh Yang4, Yaoh-Shiang Lin5,6, Yi-Han Tseng1, Chia-Lin Liu2, Tsai-Yu Lee3,7, Tsung-Yun Liu7, Yueng-Hsiang Chu6, Su-Feng Chen8. 1. Department and Graduate School of Pathology, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan. 2. Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. 3. Division of Colon and Rectal Surgery, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan. 4. Department of Dentistry, Cheng Hsin Hospital, Taipei, Taiwan. 5. Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. 6. Department of Otolaryngology-Head and Neck Surgery, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan. 7. Institute of Environmental and Occupational Health Sciences, National Yang-Ming University, Taipei, Taiwan. 8. Department of Dental Hygiene, China Medical University, Taichung, Taiwan.
Abstract
BACKGROUND: Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear. METHODS: An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial-mesenchymal transition, drug-resistance-related genes, properties of cancer stem cells (CSCs), and anti-apoptosis was performed. RESULTS: Long-term NNK exposure enhances migration and invasion with morphological alterations in a dose-dependently manner. Furthermore, NNK exposure also upregulates Snail, promotes sphere-forming ability, and overexpresses aldehyde dehydrogenase 1 (ALDH1), Nanog, OCT4, ABCG2, and MDR1. CONCLUSION: The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that α7 nicotinic acetylcholine receptor (α7-nAChR) inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC.
BACKGROUND: Recent studies suggest that long-term exposure of the carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine-mediated mechanism remains unclear. METHODS: An analysis of SCC-25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial-mesenchymal transition, drug-resistance-related genes, properties of cancer stem cells (CSCs), and anti-apoptosis was performed. RESULTS: Long-term NNK exposure enhances migration and invasion with morphological alterations in a dose-dependently manner. Furthermore, NNK exposure also upregulates Snail, promotes sphere-forming ability, and overexpresses aldehyde dehydrogenase 1 (ALDH1), Nanog, OCT4, ABCG2, and MDR1. CONCLUSION: The current study confirmed that long-term NNK exposure plays a role in HNSCC by increasing anti-apoptosis and therapeutic resistance via the Snail-RKIP signaling pathway. Our data also suggest that α7 nicotinic acetylcholine receptor (α7-nAChR) inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC.