Niclosamide(NA)overcomes cisplatin resistance in human ovarian cancer  

作　　者：Linjuan Huang Jing Zhang Youling Deng Hao Wang Piao Zhao Guozhi Zhao Wei Zeng Yonghui Wang Connie Chen William Wagstaff Rex C.Haydon Russell R.Reid Tong-Chuan He Le Shen Hue H.Luu Ling Zhao 

机构地区：[1]Departments of Obstetrics and Gynecology,Orthopaedic Surgery and Urology,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400046,China [2]Molecular Oncology Laboratory,Department of Orthopaedic Surgery and Rehabilitation Medicine,The University of Chicago Medical Center,Chicago,IL 60637,USA [3]Ministry of Education Key Laboratory of Diagnostic Medicine,and Department of Clinical Biochemistry,The School of Laboratory Medicine,Chongqing Medical University,Chongqing 400016,China [4]Department of Neurology,The Second Affiliated Hospital of Jianghan University,Wuhan,Hubei 430050,China [5]Department of Clinical Laboratory Medicine,Shanghai Jiaotong University School of Medicine,Shanghai 200000,China [6]Laboratory of Craniofacial Suture Biology and Development,Department of Surgery Section of Plastic Surgery,The University of Chicago Medical Center,Chicago,IL 60637,USA [7]Department of Surgery,The University of Chicago Medical Center,Chicago,IL 60637,USA

出　　处：《Genes & Diseases》2023年第4期1687-1701,共15页基因与疾病（英文）

基　　金：supported in part by research grants from the National Institutes of Health(No.CA226303 to TCH,No.DE030480 to RRR);supported by the Medical Scientist Training Program of the National Institutes of Health(USA)(No.T32 GM007281);supported in part by The University of Chicago Cancer Center Support Grant(No.P30CA014599);the National Center for Advancing Translational Sciences of the National Institutes of Health(USA)(No.UL1 TR000430);supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedics Alumni Fund.

摘　　要：Ovarian cancer(OC)is one of the most lethal malignancies of the female reproduc-tive system.OC patients are usually diagnosed at advanced stages due to the lack of early diag-nosis.The standard treatment for OC includes a combination of debulking surgery and platinum-taxane chemotherapy,while several targeted therapies have recently been approved for maintenance treatment.The vast majority of OC patients relapse with chemoresistant tu-mors after an initial response.Thus,there is an unmet clinical need to develop new therapeu-tic agents to overcome the chemoresistance of OC.The anti-parasite agent niclosamide(NA)has been repurposed as an anti-cancer agent and exerts potent anti-cancer activities in human cancers including OC.Here,we investigated whether NA could be repurposed as a therapeutic agent to overcome cisplatin-resistant(CR)in human OC cells.To this end,we first established two CR lines SKOV3CR and OVCAR8CR that exhibit the essential biological characteristics of cisplatin resistance in human cancer.We showed that NA inhibited cell proliferation,sup-pressed cell migration,and induced cell apoptosis in both CR lines at a low micromole range.Mechanistically,NA inhibited multiple cancer-related pathways including AP1,ELK/SRF,HIF1,and TCF/LEF,in SKOV3CR and OVCAR8CR cells.NA was further shown to effectively inhibit xenograft tumor growth of SKOV3CR cells.Collectively,our findings strongly suggest that NA may be repurposed as an efficacious agent to combat cisplatin resistance in chemoresistant hu-man OC,and further clinical trials are highly warranted.

关 键 词：Chemotherapy resistance CISPLATIN Drug repurposing NICLOSAMIDE Ovarian cancer 

分 类 号：R73[医药卫生—肿瘤]