Ropivacaine prompts ferroptosis to enhance the cisplatin-sensitivity of human colorectal cancer through SIRT1/Nrf2 signaling pathway.

Autor: Zeng L; Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China., Zhao W; Department of Anesthesiology, Central Laboratory, Hubei Clinical Research Center of Parkinson's disease, Xiangyang Key Laboratory of Movement Disorders, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 44100, China., Han T; Department of Anesthesiology, Central Laboratory, Hubei Clinical Research Center of Parkinson's disease, Xiangyang Key Laboratory of Movement Disorders, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 44100, China., Qing F; Department of Anesthesiology, Xiangyang No.1 People's Hospita, Jinzhou Medical University Union Training Base, Xiangyang, 44100, China., He Z; Department of Anesthesiology, Central Laboratory, Hubei Clinical Research Center of Parkinson's disease, Xiangyang Key Laboratory of Movement Disorders, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 44100, China., Zhao Q; Department of Anesthesiology, Central Laboratory, Hubei Clinical Research Center of Parkinson's disease, Xiangyang Key Laboratory of Movement Disorders, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 44100, China., Luo A; Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China., Hu P; Department of Anesthesiology, Central Laboratory, Hubei Clinical Research Center of Parkinson's disease, Xiangyang Key Laboratory of Movement Disorders, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 44100, China. Electronic address: hupengchao0904@126.com., Ding X; Department of Rehabilitation Medicine, Clinical Medical Center for Rehabilitation Treatment of Dystonia Disease, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 44100, China. Electronic address: dingxd1018@163.com., Zhang Z; Department of Anesthesiology, Central Laboratory, Hubei Clinical Research Center of Parkinson's disease, Xiangyang Key Laboratory of Movement Disorders, Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, 44100, China. Electronic address: xss318@163.com.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2024 Sep 01; Vol. 400, pp. 111163. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1016/j.cbi.2024.111163
Abstrakt: The ineffectiveness of cisplatin therapy in treating colorectal cancer (CRC) is attributed to an increase of resistance. It's necessary to investigate adjunctive agents capable of enhancing drug efficacy. Previous studies have shown that ropivacaine inhibit the growth of various cancer cells, but its impact on cisplatin resistance in tumors is not well understood. This study was to illustrate the impact and mechanism of ropivacaine enhanced cisplatin-sensitivity of CRC. Cisplatin alone treatment resulted in the elevation of reactive oxygen species (ROS) and intracellular Fe 2+ levels, as well as a reduction in mitochondrial membrane potential (MMP) in cisplatin-sensitive LOVO cells, while these effects were mitigated in the cisplatin-resistant LOVO/DDP cells. The co-administration of ropivacaine with cisplatin inhibited cell viability and cell migration, decreased MMP, and promoted ROS accumulation and apoptosis in both LOVO cells and LOVO/DDP cells. And they upregulated the levels of ferroptosis makers and downregulated the expression of anti-ferroptosis proteins. However, this effect was reversed by ferroptosis inhibitor ferrostatin-1 or liproxstatin-1. Furthermore, we o demonstrated that the co-administration of ropivacaine and cisplatin resulted in a decrease in SIRT1 expression, and SIRT1 knockdown in LOVO/DDP cells enhanced the ferroptosis and the anti-tumor properties of ropivacaine, while also inhibiting the activation of the Nrf2/Keap1 pathway. The above results suggested that ropivacaine increased the sensitivity of CRC cells to cisplatin by promoting ferroptosis through the inhibition of SIRT1 expression, which proposes a therapeutic approach for overcoming cisplatin resistance in CRC.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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