Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Int J Biochem Cell Biol. 2020 May;122:105732. doi: 10.1016/j.biocel.2020.105732. Epub 2020 Feb 22.
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.
顺铂是治疗舌鳞状细胞癌（TSCC）患者最常用的抗癌药物之一，但由于化疗耐药性的存在，其疗效受到限制。大量证据表明，活性氧（ROS）在多种肿瘤化疗耐药性中起着关键作用。在本研究中，我们旨在研究 ROS 在 TSCC 顺铂耐药性中的作用，并在体外探讨其潜在的分子机制。我们的结果表明，ROS 清除剂 N-乙酰半胱氨酸预处理可降低 TSCC 细胞中顺铂诱导的细胞毒性、自噬和细胞凋亡。下调细胞内 ROS 可通过逆转 p38MAPK/mTOR 通路的抑制作用，减轻 TSCC 顺铂耐药性 CAL27/CDDP 细胞的凋亡和自噬。综上所述，这些发现表明，下调细胞内 ROS 可通过抑制 p38MAPK/mTOR 介导的途径减少 TSCC 细胞中顺铂的细胞毒性，从而抑制细胞凋亡和自噬。细胞内 ROS 水平较低可能是 TSCC 中顺铂耐药的主要机制之一。
