Proteomics Analysis Revealed Smad3 as a Potential Target of the Synergistic Anti-tumor Activity of Disulfiram and Cisplatin in Ovarian Cancer

doi:10.2174/1871520623666230516161200

	Proteomics Analysis Revealed Smad3 as a Potential Target of the Synergistic Anti-tumor Activity of Disulfiram and Cisplatin in Ovarian Cancer
	Du, Ruiping 6,7; Sun, Feilong 5,6; Li, Kai 4; Qi, Jian 5,6; Zhong, Wen 2,3; Wang, Wei 2,3; Sun, Qiuyan 1,6; Deng, Qingmei 1,6; Wang, Hongzhi 1,6; Nie, Jinfu 1,6
刊名	ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
	2023
卷号	23
关键词	Disulfiram cisplatin resistance ovarian cancer proteomics analysis SMAD3 lactate dehydrogenase
ISSN号	1871-5206
DOI	10.2174/1871520623666230516161200
通讯作者	Ding, Chen(bhong@hmfl.ac.cn) ; Hong, Bo(chend@fudan.edu.cn)
英文摘要	Introduction Among gynecological cancers, ovarian cancer has a high mortality rate. Cisplatin-based chemotherapy is commonly used for the treatment of ovarian cancer. However, the clinical efficacy of cisplatin in ovarian cancer is limited due to the development of chemo-resistance during treatment.Objective In the study, we aimed to investigate the synergistic anti-cancer activity and targets of the FDA-approved drug disulfiram combined with cisplatin in ovarian cancer.Methods The cell viability was determined by Celltier-Glo luminescent assay. The synergistic anti-cancer activity was assessed by combination index. Cell cycle and apoptosis were detected by flow cytometry. The in vivo anti-tumor activity and side effects were evaluated using a xenografted mice model. The synergistic anti-cancer targets were identified by a mass spectrometry-based proteomics analysis.Results In this study, we first found that disulfiram synergistically enhanced the anti-tumor activity of cisplatin in chemo-resistant ovarian cancer cells, which was accompanied by the enhanced induction of cellular apoptosis. Secondly, the in vivo study demonstrated that the combination treatment of disulfiram and cisplatin dramatically inhibited tumor growth and had no apparent side effects in ovarian cancer xenografted mice. Finally, proteomics analysis identified SMAD3 as a potential target of disulfiram-cisplatin combined treatment, and the down-regulation of SMAD3 could increase cisplatin-induced cell death in ovarian cancer.Conclusion Combination treatment of disulfiram and cisplatin synergistically inhibited the growth of ovarian cancer through down-regulating SMAD3. As a repurposed drug, disulfiram could be quickly transformed into a clinic to overcome cisplatin resistance for the treatment of ovarian cancer.
资助项目	Declared none.
WOS关键词	BLADDER-CANCER ; DRUG ; RESISTANCE
WOS研究方向	Oncology ; Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:001064314200007
资助机构	Declared none.
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/132649]
专题	中国科学院合肥物质科学研究院
通讯作者	Ding, Chen; Hong, Bo
作者单位	1.Chinese Acad Sci, Hefei Canc Hosp, Hefei, Anhui, Peoples R China 2.Univ Sci & Technol China, Intelligent Pathol Inst, Div Life Sci & Med, Hefei, Anhui, Peoples R China 3.Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Pathol, Div Life Sci & Med, Hefei, Anhui, Peoples R China 4.Fudan Univ, Inst Biomed Sci, Sch Life Sci, State Key Lab Genet Engn,Human Phenome Inst,Zhongs, Shanghai 200433, Peoples R China 5.Univ Sci & Technol China, Hefei, Anhui, Peoples R China 6.Chinese Acad Sci, Anhui Prov Key Lab Med Phys & Technol, Inst Hlth & Med Technol, Hefei Inst Phys Sci, Hefei, Anhui, Peoples R China 7.Anhui Med Univ, Sch Basic Med Sci, Hefei, Peoples R China
推荐引用方式 GB/T 7714	Du, Ruiping,Sun, Feilong,Li, Kai,et al. Proteomics Analysis Revealed Smad3 as a Potential Target of the Synergistic Anti-tumor Activity of Disulfiram and Cisplatin in Ovarian Cancer[J]. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY,2023,23.
APA	Du, Ruiping.,Sun, Feilong.,Li, Kai.,Qi, Jian.,Zhong, Wen.,...&Hong, Bo.(2023).Proteomics Analysis Revealed Smad3 as a Potential Target of the Synergistic Anti-tumor Activity of Disulfiram and Cisplatin in Ovarian Cancer.ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY,23.
MLA	Du, Ruiping,et al."Proteomics Analysis Revealed Smad3 as a Potential Target of the Synergistic Anti-tumor Activity of Disulfiram and Cisplatin in Ovarian Cancer".ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY 23(2023).