Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy; Clinic of Obstetrics and Gynaecology, Department of Clinical Sciences, Università Politecnica delle Marche, Salesi Hospital, Azienda Ospedaliero Universitaria, Ancona, Italy.
Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60126 Ancona, Italy.
Pharmacol Res. 2022 Sep;183:106365. doi: 10.1016/j.phrs.2022.106365. Epub 2022 Jul 25.
Among gynecologic malignancies, ovarian cancer is one of the most dangerous, with a high fatality rate and relapse due to the occurrence of chemoresistance. Many researchers demonstrated that oxidative stress is involved in tumor occurrence, development and procession. Nuclear factor erythroid 2-related factor 2 (NRF2) is an important transcription factor playing an important role in protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) activate NRF2 signaling inducing the expression of antioxidant enzymes such as heme oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) that protect cells against oxidative stress. However, NRF2 activation in cancer cells is responsible for the development of chemoresistance inactivating drug-mediated oxidative stress that normally leads cancer cells to death. In this review we analyzed the current literature regarding the role of natural and synthetic compounds in modulating NRF2/KEAP1 (Kelch Like ECH Associated Protein 1) pathway in in vitro models of ovarian cancer. In particular, we reported how these compounds can modulate chemotherapy response.
在妇科恶性肿瘤中，卵巢癌是最危险的癌症之一，由于发生化疗耐药，其死亡率和复发率都很高。许多研究人员表明，氧化应激与肿瘤的发生、发展和进程有关。核因子红细胞 2 相关因子 2（NRF2）是一种重要的转录因子，在保护氧化损伤方面发挥着重要作用。活性氧（ROS）水平的增加会激活 NRF2 信号通路，诱导抗氧化酶如血红素加氧酶（HO-1）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）的表达，从而保护细胞免受氧化应激。然而，癌细胞中 NRF2 的激活导致了化疗耐药的发展，使药物介导的氧化应激失活，通常导致癌细胞死亡。在这篇综述中，我们分析了关于天然和合成化合物在调节卵巢癌细胞体外模型中的 NRF2/KEAP1（Kelch 样 ECH 相关蛋白 1）通路的作用的最新文献。特别地，我们报告了这些化合物如何调节化疗反应。
