ROS enhances the cytotoxicity of cisplatin by inducing apoptosis and autophagy in tongue squamous cell carcinoma cells
ROS enhances the cytotoxicity of cisplatin by inducing apoptosis and autophagy in tongue squamous cell carcinoma cells
复制标题
ROS通过诱导舌鳞状细胞癌细胞凋亡和自噬增强顺铂的细胞毒性
DOI：
10.1016/j.biocel.2020.105732
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发表时间：
2020-05-01
影响因子：
4
通讯作者：
Qiu, Jia-Xuan
中科院分区：
文献类型：
--
作者：
Xue, Dan-Feng;Pan, Shu-Ting;Qiu, Jia-Xuan
顺铂是治疗舌鳞状细胞癌(TSCC)应用最广泛的抗癌药物之一，但其疗效受到化疗耐药性的限制。越来越多的证据表明，活性氧(ROS)在肿瘤多药耐药中起重要作用。本研究旨在探讨ROS在舌鳞癌顺铂耐药中的作用，并探讨其可能的分子机制。我们的结果表明，ROS清除剂N-乙酰半胱氨酸的预处理减少了顺铂诱导的细胞毒性、自噬和TSCC细胞凋亡。下调细胞内ROS可逆转p38MAPK/mTOR通路的抑制作用，从而减轻对顺铂耐药的CAL27/CDDP细胞的凋亡和自噬。综上所述，这些发现提示，细胞内ROS的下调可能通过抑制p38MAPK/mTOR途径抑制TSCC细胞的凋亡和自噬，从而降低顺铂的细胞毒性。细胞内ROS水平低可能是TSCC对顺铂耐药的主要机制之一。
Cisplatin is one of the most widely used anticancer agents for patients with tongue squamous cell carcinoma (TSCC), but its efficacy is limited by chemoresistance. Accumulated evidence has demonstrated that reactive oxygen species (ROS) plays a critical role in multiple tumor chemotherapy resistance. In the present study, we aimed to investigate the role of ROS in cisplatin resistance of TSCC and explore its underlying molecular mechanism in vitro. Our results showed that pre-treatment with ROS scavenger N-acetylcysteine reduced cisplatin-induced cytotoxicity, autophagy, and apoptosis in TSCC cells. Down-regulation of intracellular ROS attenuated apoptosis and autophagy of TSCC cisplatin-resistant CAL27/CDDP cells by reversing the inhibition of p38MAPK/mTOR pathway. Taken together, these findings suggest that down-regulation of intracellular ROS reduces the cytotoxicity of cisplatin by inhibiting apoptosis and autophagy in TSCC cells involving p38MAPK/mTOR mediated pathway. Low intracellular ROS levels may be one of the main mechanisms of cisplatin resistance in TSCC.