顺铂是一种广泛使用的化疗药物，它与DNA相互作用形成Pt-DNA加合物，导致DNA双链断裂和细胞凋亡。耐药性是顺铂临床应用的主要障碍。合成并表征了基于喹啉衍生物的 Pt(II) 配合物 PtQ。作为顺铂的类似物，PtQ 在卵巢癌中表现出一种新的抗癌机制。 PtQ 导致活性氧 (ROS) 产生过多，从而引发卵巢癌中的铁死亡细胞。胱氨酸/谷氨酸逆向转运蛋白 SLC7A11 和缓解脂质过氧化的谷胱甘肽过氧化物酶 4 (GPX4) 在 PtQ 处理的 SKOV3 细胞中均下调。此外，PtQ 诱导 DNA 单链断裂并抑制单链断裂修复蛋白 PARP1 的表达。机制研究表明，PtQ 有望绕过卵巢癌顺铂耐药介导的信号通路。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Cisplatin is a widely used chemotherapeutic agent which interacts with DNA to form Pt-DNA adducts, leading to DNA double-strand breaks and apoptosis. Resistance is the major obstacle in the clinical application of cisplatin. A quinoline derivative based Pt(II) complex PtQ was synthesized and characterized. As an analogue of cisplatin, PtQ demonstrated a novel anticancer mechanism in ovarian cancer. PtQ caused excessive production of reactive oxygen species (ROS), which triggered ferroptotic cell death in ovarian cancer. Cystine/glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4) which alleviate lipid peroxidation were both downregulated in PtQ-treated SKOV3 cells. Furthermore, PtQ induced DNA single-strand breaks and suppressed the expression of single-strand breaks repair protein PARP1. Mechanism studies demonstrated that PtQ can hopefully bypass the signaling pathways mediated cisplatin resistance in ovarian cancer.Copyright © 2024 Elsevier Inc. All rights reserved.