Qiu Mingning, Zhang Sai, Ke Longzhi, Tang Huancheng, Zeng Xin, Liu Jianjun
Laboratory of Urology, Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China.
Oncol Lett. 2019 Jan;17(1):757-764. doi: 10.3892/ol.2018.9684. Epub 2018 Nov 9.
The aim of the present study was to investigate the influence of the nitric oxide donor prodrug JS-K (CHNO) on Taxol-induced apoptosis in prostate cancer cells, and to investigate a potential reactive oxygen species (ROS)-associated mechanism. The effect of JS-K on the anticancer activity of Taxol was assessed in prostate cancer cells; cell viability, colony formation, apoptosis, ROS generation and expression levels of apoptosis-associated proteins were investigated. The function of ROS accumulation in the combined effects of JS-K and Taxol was determined using the antioxidant N-acetylcysteine (NAC) and the pro-oxidant oxidized glutathione (GSSG). The results of the present study demonstrated that JS-K was able to increase Taxol-induced suppression of prostate cancer cell proliferation, apoptosis, ROS accumulation and upregulation of apoptosis-associated proteins. Furthermore, NAC reversed the effect of JS-K on Taxol-induced apoptosis and conversely, the pro-oxidant GSSG exacerbated the effect of JS-K on Taxol-induced apoptosis in prostate cancer cells. In conclusion, JS-K enhances the chemosensitivity of prostate cancer cells to Taxol, via the upregulation of intracellular ROS.
本研究的目的是探讨一氧化氮供体前药JS-K（CHNO）对紫杉醇诱导前列腺癌细胞凋亡的影响，并研究一种潜在的活性氧（ROS）相关机制。在前列腺癌细胞中评估了JS-K对紫杉醇抗癌活性的影响；研究了细胞活力、集落形成、凋亡、ROS生成以及凋亡相关蛋白的表达水平。使用抗氧化剂N-乙酰半胱氨酸（NAC）和促氧化剂氧化型谷胱甘肽（GSSG）确定了ROS积累在JS-K和紫杉醇联合作用中的功能。本研究结果表明，JS-K能够增强紫杉醇诱导的对前列腺癌细胞增殖的抑制作用、凋亡、ROS积累以及凋亡相关蛋白的上调。此外，NAC逆转了JS-K对紫杉醇诱导凋亡的作用，相反，促氧化剂GSSG加剧了JS-K对前列腺癌细胞中紫杉醇诱导凋亡的作用。总之，JS-K通过上调细胞内ROS增强了前列腺癌细胞对紫杉醇的化学敏感性。
