Huang Wei, Ren Caiping, Huang Guoling, Liu Jie, Liu Weidong, Wang Lei, Zhu Bin, Feng Xiangling, Shi Jia, Li Jinlong, Xia Xiaomeng, Jia Wei, Chen Jiawen, Chen Yuxiang, Jiang Xingjun
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China; Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Xiangya Hospital, Changsha, Hunan 410008, P.R. China; Cancer Research Institute, Collaborative Innovation Center for Cancer Medicine, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, P.R. China.
Oncol Lett. 2017 Feb;13(2):921-929. doi: 10.3892/ol.2016.5469. Epub 2016 Dec 7.
Sodium butyrate (NaBu), a histone deacetylase inhibitor, has demonstrated anti-tumor effects in several cancers, and is a promising candidate chemotherapeutic agent. However, its roles in nasopharyngeal carcinoma (NPC), an endemic malignant disease in Southern China and Southeast Asia, has rarely been studied. In the present study, MTT assay, colony formation assay, flow cytometry analysis and western blotting were performed to explore the influence of NaBu on NPC cells and its underlying mechanism. NaBu induced morphological changes and inhibited proliferation in 5-8F and 6-10B cells. MTT assay revealed that NaBu was cytotoxic to 5-8F and 6-10B cells in a dose- and time-dependent manner. Furthermore, flow cytometry analysis revealed that NaBu induced obvious cell apoptosis in 5-8F and 6-10B cells due to the activation of the mitochondrial apoptosis axis. In addition, flow cytometry analysis and western blotting demonstrated that NaBu could enhance the Ca influx by promoting store-operated Ca entry (SOCE) in 5-8F and 6-10B cells. Inhibition of SOCE by specific inhibitors or downregulated expression of calcium release-activated calcium channel protein 1 and stromal interaction molecule 1 could counteract the apoptosis of NPC cells induced by NaBu. Thus, the current study revealed that enhanced SOCE and activated mitochondrial apoptosis axis may account for the mechanisms of cytotoxicity of NaBu in NPC cells, and that NaBu serves as a promising chemotherapeutic agent in NPC therapy.
丁酸钠（NaBu）是一种组蛋白去乙酰化酶抑制剂，已在多种癌症中显示出抗肿瘤作用，是一种很有前景的化疗候选药物。然而，其在中国南方和东南亚地区的地方性恶性疾病鼻咽癌（NPC）中的作用鲜有研究。在本研究中，进行了MTT法、集落形成试验、流式细胞术分析和蛋白质印迹法，以探讨NaBu对NPC细胞的影响及其潜在机制。NaBu诱导5-8F和6-10B细胞发生形态变化并抑制其增殖。MTT法显示，NaBu对5-8F和6-10B细胞具有剂量和时间依赖性的细胞毒性。此外，流式细胞术分析显示，由于线粒体凋亡轴的激活，NaBu诱导5-8F和6-10B细胞发生明显的细胞凋亡。此外，流式细胞术分析和蛋白质印迹法表明，NaBu可通过促进5-8F和6-10B细胞中的储存式钙内流（SOCE）来增强钙内流。用特异性抑制剂抑制SOCE或下调钙释放激活钙通道蛋白1和基质相互作用分子1的表达可抵消NaBu诱导的NPC细胞凋亡。因此，本研究表明，增强的SOCE和激活的线粒体凋亡轴可能是NaBu对NPC细胞产生细胞毒性的机制，并且NaBu在NPC治疗中是一种有前景的化疗药物。
