Fang‐Wei Hu1,2, Lo‐Lin Tsai1,2, Chuan‐Hang Yu1,2, Pei‐Ni Chen3, Ming‐Yung Chou1,4,2, Cheng‐Chia Yu1,4,2
1Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan
2School of Dentistry, Chung Shan Medical University, Taichung, Taiwan
3Institute of Biochemistry, Chung Shan Medical University, Taichung, Taiwan
4Institute of Oral Science, Chung Shan Medical University, Taichung, Taiwan
Tóm tắt
ScopeRecent reports have demonstrated that head and neck cancer‐derived tumor‐initiating cells (HNC‐TICs) presented high tumorigenic, chemoradioresistant, metastatic properties, and were coupled with gain of epithelial–mesenchymal transition (EMT) characteristics. The aim of this study was to investigate the chemotherapeutic effect and regulatory mechanisms of resveratrol on HNC‐TICs.Methods and resultsWe first observed that the treatment of resveratrol significantly downregulated the ALDH1 activity and CD44 positivity of head and neck cancer (HNC) cells in a dose‐dependent manner (p < 0.05). Moreover, resveratrol treatment reduced self‐renewal property and stemness genes signatures (Oct4, Nanog, and Nestin) expression in sphere‐forming HNC‐TICs. Additionally, the repressive effect of resveratrol on in vitro malignant properties including invasiveness/anchorage‐independent growth was mediated by regulating productions of EMT markers Slug, ZEB1, N‐cadherin, E‐cadherin, and Vimentin. Importantly, an in vivo nude mice model showed that resveratrol treatment to xenograft tumors by oral gavage reduced tumor growth, stemness, and EMT markers in vivo. Lastly, synergistic effect of resveratrol and conventional chemotreatment attenuated tumor‐initiating cells property in HNC‐TICs.ConclusionsOur results demonstrated that resveratrol would be a valuable therapeutics clinically in combination with conventional chemotherapy treatment modalities for malignant HNCs by elimination of tumor‐initiating stem‐like and EMT properties.
