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.

顺铂是用于舌鳞状细胞癌（TSCC）患者的最广泛使用的抗癌药之一，但其疗效受到化学耐药性的限制。积累的证据表明，活性氧（ROS）在多种肿瘤化疗耐药性中起关键作用。在本研究中，我们旨在研究ROS在TSCC顺铂耐药中的作用，并探讨其在体外的潜在分子机制。。我们的结果表明，用ROS清道夫N-乙酰半胱氨酸预处理可减少顺铂诱导的TSCC细胞毒性，自噬和凋亡。通过逆转对p38MAPK / mTOR通路的抑制，细胞内ROS的下调减弱了TSCC顺铂耐药CAL27 / CDDP细胞的凋亡和自噬。综上所述，这些发现表明，细胞内ROS的下调通过抑制涉及p38MAPK / mTOR介导的途径的TSCC细胞的凋亡和自噬而降低了顺铂的细胞毒性。细胞内ROS水平低可能是TSCC中顺铂耐药的主要机制之一。