Evidence map›Paper›PMID 42374476›Full record

ArticleCell communication and signaling : CCS2026

Targeting AIF to trigger RIPKs/MLKL necroptosis: a disulfiram-based strategy to reverse paclitaxel resistance in ovarian cancer.

Jiaofeng Li, Wei Zhou, Hualong Tang, Wanglong Zhu, Miao He, Qing Xiong, Zhengyu Han, Xinyue Lin, Ji Chen, Xingqiang He and 7 more

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In one paragraph

Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

17 authors.

Jiaofeng Li *The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Wei Zhou *The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Hualong Tang *The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Wanglong Zhu *The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Miao HeThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Qing XiongThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Zhengyu HanThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Xinyue LinThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Ji ChenThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Xingqiang HeSchool of Laboratory Medicine, Chengdu Medical College, Chengdu, 610500, China.
Mei ChenThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Yuhan YangThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Xia MengThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Liping MaThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China.
Fengtian LiThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China. lft549544593@live.com.
Jingyi WangThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China. wjy416h@163.com.
Kun ZhangThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital; The Affiliated Cancer Hospital of Chengdu Medical College, Chengdu Seventh People's Hospital; School of Bioscience and Technology, Chengdu Medical College, Chengdu, 610500, China. zhangkunyyo@cmc.edu.cn.ORCID http://orcid.org/0000-0001-5891-0400

Funding

Clinical Science Research Foundations of Collaborative Innovation Center of Sichuan for Elderly Care and Health 2022LHTD-02CMC Excellent-talent Program 2024kjTzn03Development and Regeneration Key Lab of Sichuan Province 24LHFYSZ1-27National Natural Science Foundation of China 82272658 and 81872451Organized Research Projects of Chengdu Medical College CYYZZ24-01Sichuan Higher Education Institute Key Laboratory of Major Disease Target Discovery and Protein Drug Development 23LHNBZZD07, 24LHBBYY1-08, 24LHBBYY1-09Sichuan Science and Technology Program 2022JDRC0042 and 2022NSFSC0777
6 · The paper itself

Abstract

objectivePaclitaxel is a cornerstone first-line therapy for ovarian cancer, but its efficacy is limited by chemoresistance. Disulfiram (DSF), an FDA-approved alcohol-aversion drug, shows promising antitumor activity. However, its impact on paclitaxel sensitivity in ovarian cancer and the underlying mechanism remain unclear.

methodsThis study identified DSF as a reversal agent of paclitaxel resistance. In vitro, DSF's chemosensitizing effect was tested on paclitaxel-resistant and parent ovarian cancer cells. Mechanistic investigations involved examining the triggering of RIPK1/RIPK3/MLKL-regulated necroptosis versus caspase-dependent apoptosis, depending on cellular context. RIPK1 was inhibited with Nec-1, and the direct binding to Apoptosis-inducing factor (AIF) was studied, with AIF knockdown used for validation. In vivo studies were conducted using resistant xenograft models to confirm the anticancer efficacy and observe necroptosis markers.

resultsDSF significantly improved paclitaxel chemosensitivity in vitro. Mechanistically, it selectively triggered necroptosis in paclitaxel-resistant cells with higher caspase-8 expression, while promoting apoptosis in cells with lower caspase-8 expression. RIPK1 inhibition impaired DSF-induced necroptosis and chemosensitization. Furthermore, DSF directly bound to AIF, enhancing RIPK1/RIPK3/MLKL phosphorylation and necroptosis activation; this effect was suppressed by AIF knockdown. Crucially, in vivo studies confirmed that DSF boosted the anticancer efficacy of paclitaxel in resistant models, which was accompanied by upregulation of the necroptosis executor p-MLKL and no observable toxicity.

conclusionOur findings not only unveiled a novel mechanistic basis for the repurposing of DSF but also highlighted AIF-mediated necroptosis as a promising therapeutic strategy to overcome chemoresistance in ovarian cancer.

Indexed as

Apoptosis Inducing FactorDisulfiramDrug Resistance, NeoplasmNecroptosisOvarian NeoplasmsPaclitaxelProtein KinasesReceptor-Interacting Protein Serine-Threonine KinasesAnimalsApoptosisCell Line, TumorFemaleHumansMiceMice, NudeApoptosis Inducing FactorDisulfiramMLKL protein, humanPaclitaxelProtein KinasesReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, humanDisulfiramNecroptosisOvarian cancerPaclitaxelResistance

Identifiers

PMID42374476
PMCPMC13584500

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.