The apoptotic effect of Zoledronic acid on the nasopharyngeal carcinoma cells via ROS mediated chloride channel activation

作者：Liang Wang, Liang Wang, Hong Gao, Yang Xiao-ya, Xiechou Liang, Qiuchan Tan, Zhanru Chen, Chan Zhao, Zhuoyu Gu, Meisheng Yu, Yanfang Zheng, Yanqing Huang, Linyan Zhu, T.J.C. Jacob, Liwei Wang, Liwei Wang, Lixin Chen · 发表于：Clinical and Experimental Pharmacology and Physiology · 年份：2018 · DOI：10.1111/1440-1681.12979 · 被引用次数：12 · 研究领域：Ion channel regulation and function、Bone health and treatments、Cell death mechanisms and regulation

Zoledronic acid (ZA), a third-generation bisphosphonate, has been applied for treatment of bone metastases caused by malignant tumors. Recent studies have found its anti-cancer effects on various tumor cells. One of the mechanisms of anti-cancer effects of ZA is induction of apoptosis. However, the mechanisms of ZA-induced apoptosis in tumor cells have not been clarified clearly. In this study, we investigated the roles of chloride channels in ZA-induced apoptosis in nasopharyngeal carcinoma CNE-2Z cells. Apoptosis and chloride current were induced by ZA and suppressed by chloride channel blockers. After the knockdown of ClC-3 expression by ClC-3 siRNA, ZA-induced chloride current and apoptosis were significantly suppressed, indicating that the chloride channel participated in ZA-induced apoptosis may be ClC-3. When reactive oxygen species (ROS) generation was inhibited by the antioxidant N-acetyl-L-cysteine (L-NAC), ZA-induced apoptosis and chloride current were blocked accordingly, suggesting that ZA induces apoptosis through promoting ROS production and subsequently activating chloride channel.