Melatonin Inhibits Reactive Oxygen Species‐Driven Proliferation, Epithelial‐Mesenchymal Transition, and Vasculogenic Mimicry in Oral Cancer

作者：Rui Liu, Hui-li Wang, Manjing Deng, Xiujie Wen, Yuanyuan Mo, Fa‐Ming Chen, Chun-li Zou, Wei-feng Duan, Li Lei, Xin Nie · 发表于：Oxidative Medicine and Cellular Longevity · 年份：2018 · DOI：10.1155/2018/3510970 · 被引用次数：63 · 研究领域：Hydrogen's biological and therapeutic effects、Dietary Effects on Health、Circadian rhythm and melatonin

Globally, oral cancer is the most common type of head and neck cancers. Melatonin elicits inhibitory effects on oral cancer; however, the biological function of melatonin and underlying mechanisms remain largely unknown. In this study, we found that melatonin impaired the proliferation and apoptosis resistance of oral cancer cells by inactivating ROS‐dependent Akt signaling, involving in downregulation of cyclin D1, PCNA, and Bcl‐2 and upregulation of Bax. Melatonin inhibited the migration and invasion of oral cancer cells by repressing ROS‐activated Akt signaling, implicating with the reduction of Snail and Vimentin and the enhancement of E‐cadherin. Moreover, melatonin hampered vasculogenic mimicry of oral cancer cells through blockage of ROS‐activated extracellular‐regulated protein kinases (ERKs) and Akt pathways involving the hypoxia‐inducible factor 1 α . Consistently, melatonin retarded tumorigenesis of oral cancer in vivo . Overall, these findings indicated that melatonin exerts antisurvival, antimotility, and antiangiogenesis effects on oral cancer partly by suppressing ROS‐reliant Akt or ERK signaling.