Yan Xiao-Yu, Qu Xian-Zhi, Xu Long, Yu Si-Hang, Tian Rui, Zhong Xin-Ru, Sun Lian-Kun, Su Jing
1Department of Pathophysiology, Key Laboratory of Pathobiology, Ministry of Education, College of Basic Medical Sciences, Jilin University, 126 Xinmin Street, Changchun, 130021 China.
2Department of Hepatobiliary & Pancreatic Surgery, The Second Hospital of Jilin University, Jilin University, Changchun, 130021 Jilin China.
Cancer Cell Int. 2020 Apr 16;20:128. doi: 10.1186/s12935-020-01196-w. eCollection 2020.
Cisplatin is a platinum-based first-line drug for treating ovarian cancer. However, chemotherapy tolerance has limited the efficacy of cisplatin for ovarian cancer patients. Research has demonstrated that cisplatin causes changes in cell survival and death signaling pathways through its interaction with macromolecules and organelles, which indicates that investigation into the DNA off-target effects of cisplatin may provide critical insights into the mechanisms underlying drug resistance. The multifunctional protein p62 works as a signaling hub in the regulation of pro-survival transcriptional factors NF-κB and Nrf2 and connects autophagy and apoptotic signals, which play important roles in maintaining cell homeostasis. In this review, we discuss the role of p62 in cisplatin resistance by exploring p62-associated signaling pathways based on current studies and our work. Insights into these resistance mechanisms may lead to more effective therapeutic strategies for ovarian cancer by targeting p62.
顺铂是治疗卵巢癌的一线铂类药物。然而，化疗耐受性限制了顺铂对卵巢癌患者的疗效。研究表明，顺铂通过与大分子和细胞器相互作用导致细胞存活和死亡信号通路发生变化，这表明对顺铂的DNA非靶向效应进行研究可能为耐药机制提供关键见解。多功能蛋白p62在促生存转录因子NF-κB和Nrf2的调控中作为信号枢纽发挥作用，并连接自噬和凋亡信号，这些信号在维持细胞稳态中起重要作用。在本综述中，我们基于当前研究和我们的工作，通过探索与p62相关的信号通路，讨论p62在顺铂耐药中的作用。对这些耐药机制的深入了解可能通过靶向p62为卵巢癌带来更有效的治疗策略。
