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1.海南医科大学第二附属医院妇科,海南 海口 570100
2.海南医科大学第二临床学院,海南 海口 570100
邓青春,E-mail:qingchun0503@163.com
收稿日期:2024-10-25,
纸质出版日期:2025-05-25
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蔡苗苗,范雅丹,邓青春.铜死亡在卵巢癌中的研究进展[J].局解手术学杂志,2025,34(05):452-457.
CAI Miao-miao,FAN Ya-dan,DENG Qing-chun.Research progress of cuproptosis in ovarian cancer[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(05):452-457.
蔡苗苗,范雅丹,邓青春.铜死亡在卵巢癌中的研究进展[J].局解手术学杂志,2025,34(05):452-457. DOI: 10.11659/jjssx.10E024101.
CAI Miao-miao,FAN Ya-dan,DENG Qing-chun.Research progress of cuproptosis in ovarian cancer[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2025,34(05):452-457. DOI: 10.11659/jjssx.10E024101.
卵巢癌作为妇科三大恶性肿瘤之一,病死率较高,传统辅助化疗由于存在高耐药性,未能显著提高晚期患者生存率,故迫切需要新的治疗手段介入以提高患者生存率。铜死亡是一种被新提出的细胞死亡形式,其是由铜超载诱导硫辛酰化蛋白聚集及Fe-S簇蛋白丢失引起,有望作为新的卵巢癌治疗手段改善患者预后。已有相关研究表明,铜死亡相关基因在卵巢癌中存在差异性表达,可指导个性化免疫治疗,参与化疗耐药。本文将对铜死亡相关机制与卵巢癌的相关性进行综述,探讨其是否能为未来卵巢癌的治疗提供新思路。
Ovarian cancer, as one of the three major malignant tumors in gynecology, has a relatively high mortality rate. Traditional adjuvant chemotherapy has failed to significantly improve the survival rate of patients in the advanced stage due to its high drug resistance. Therefore, new treatment methods are urgently needed to improve the survival rate of patients.Cuproposis is a newly proposed form of cell death,which is caused by the accumulation of lipoylated protein and the loss of Fe-S cluster protein by copper overload, and it is expected to be a new treatment method for ovarian cancer to improve the prognosis of patients.Previous studies have shown that cuproptosis related genes are differentially expressed in ovarian cancer,which can guide personalized immunotherapy and participate in chemotherapy resistance.This article will review the correlation between the mechanisms related to cuproptosis and ovarian cancer,and explore whether it can provide new ideas for the treatment of ovarian cancer in the future.
Terp SK , Stoico MP , Dybkaer K , et al . Early diagnosis of ovarian cancer based on methylation profiles in peripheral blood cell-free DNA:a systematic review [J]. Clin Epigenetics , 2023 , 15 ( 1 ): 24 . doi: 10.1186/s13148-023-01440-w http://dx.doi.org/10.1186/s13148-023-01440-w .
Siegel RL , Miller KD , Wagle NS , et al . Cancer statistics,2023 [J]. CA Cancer J Clin , 2023 , 73 ( 1 ): 17 - 48 . doi: 10.3322/caac.21763 http://dx.doi.org/10.3322/caac.21763 .
Tsvetkov P , Coy S , Petrova B , et al . Copper induces cell death by targeting lipoylated TCA cycle proteins [J]. Science , 2022 , 375 ( 6586 ): 1254 - 1261 . doi: 10.1126/science.abf0529 http://dx.doi.org/10.1126/science.abf0529 .
Wang Y , Zhang L , Zhou F . Cuproptosis:a new form of programmed cell death [J]. Cell Mol Immunol , 2022 , 19 ( 8 ): 867 - 868 . doi: 10.1038/s41423-022-00866-1 http://dx.doi.org/10.1038/s41423-022-00866-1 .
Chen L , Min J , Wang F . Copper homeostasis and cuproptosis in health and disease [J]. Signal Transduct Target Ther , 2022 , 7 ( 1 ): 378 . doi: 10.1038/s41392-022-01229-y http://dx.doi.org/10.1038/s41392-022-01229-y .
Galler T , Lebrun V , Raibaut L , et al . How trimerization of CTR1 N-terminal model peptides tunes Cu-binding and redox-chemistry [J]. Chem Commun (Camb) , 2020 , 56 ( 81 ): 12194 - 12197 . doi: 10.1039/d0cc04693k http://dx.doi.org/10.1039/d0cc04693k .
Ramos D , Mar D , Ishida M , et al . Mechanism of copper uptake from blood plasma ceruloplasmin by mammalian cells [J]. PLoS One , 2016 , 11 ( 3 ): e0149516 . doi: 10.1371/journal.pone.0149516 http://dx.doi.org/10.1371/journal.pone.0149516 .
Bhattacharjee A , Chakraborty K , Shukla A . Cellular copper homeostasis:current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases [J]. Metallomics , 2017 , 9 ( 10 ): 1376 - 1388 . doi: 10.1039/c7mt00066a http://dx.doi.org/10.1039/c7mt00066a .
Spiers JG , Tan LS , Anderson ST , et al . Hepatic homeostasis of metal ions following acute repeated stress exposure in rats [J]. Antioxidants (Basel) , 2021 , 11 ( 1 ): 85 . doi: 10.3390/antiox11010085 http://dx.doi.org/10.3390/antiox11010085 .
Chan WY , Garnica AD , Rennert OM . Cell culture studies of Menkes kinky hair disease [J]. Clin Chim Acta , 1978 , 88 ( 3 ): 495 - 507 . doi: 10.1016/0009-8981(78)90284-x http://dx.doi.org/10.1016/0009-8981(78)90284-x .
Solmonson A , DeBerardinis RJ . Lipoic acid metabolism and mitochondrial redox regulation [J]. J Biol Chem , 2018 , 293 ( 20 ): 7522 - 7530 . doi: 10.1074/jbc.TM117.000259 http://dx.doi.org/10.1074/jbc.TM117.000259 .
Patel MS , Nemeria NS , Furey W , et al . The pyruvate dehydrogenase complexes:structure-based function and regulation [J]. J Biol Chem , 2014 , 289 ( 24 ): 16615 - 16623 . doi: 10.1074/jbc.R114.563148 http://dx.doi.org/10.1074/jbc.R114.563148 .
Cobine PA , Brady DC . Cuproptosis:cellular and molecular mechanisms underlying copper-induced cell death [J]. Mol Cell , 2022 , 82 ( 10 ): 1786 - 1787 . doi: 10.1016/j.molcel.2022.05.001 http://dx.doi.org/10.1016/j.molcel.2022.05.001 .
Ishida S , Andreux P , Poitry-Yamate C , et al . Bioavailable copper modulates oxidative phosphorylation and growth of tumors [J]. Proc Natl Acad Sci U S A , 2013 , 110 ( 48 ): 19507 - 19512 . doi: 10.1073/pnas.1318431110 http://dx.doi.org/10.1073/pnas.1318431110 .
Yaman M , Kaya G , Simsek M . Comparison of trace element concentrations in cancerous and noncancerous human endometrial and ovary tissues [J]. Int J Gynecol Cancer , 2007 , 17 ( 1 ): 220 - 228 . doi: 10.1111/j.1525-1438.2006.00742.x http://dx.doi.org/10.1111/j.1525-1438.2006.00742.x .
Zowczak M , Iskra M , Torlinski L , et al . Analysis of serum copper and zinc concentrations in cancer patients [J]. Biol Trace Elem Res , 2001 , 82 ( 1/3 ): 1 - 8 . doi: 10.1385/BTER:82:1-3:001 http://dx.doi.org/10.1385/BTER:82:1-3:001 .
Anderson NM , Mucka P , Kern JG , et al . The emerging role and targetability of the TCA cycle in cancer metabolism [J]. Protein Cell , 2018 , 9 ( 2 ): 216 - 237 . doi: 10.1007/s13238-017-0451-1 http://dx.doi.org/10.1007/s13238-017-0451-1 .
Blockhuys S , Celauro E , Hildesjo C , et al . Defining the human copper proteome and analysis of its expression variation in cancers [J]. Metallomics , 2017 , 9 ( 2 ): 112 - 123 . doi: 10.1039/c6mt00202a http://dx.doi.org/10.1039/c6mt00202a .
Lelievre P , Sancey L , Coll JL , et al . The multifaceted roles of copper in cancer:a trace metal element with dysregulated metabolism,but also a target or a bullet for therapy [J]. Cancers (Basel) , 2020 , 12 ( 12 ): 3594 . doi: 10.3390/cancers12123594 http://dx.doi.org/10.3390/cancers12123594 .
Lin X , Okuda T , Holzer A , et al . The copper transporter CTR1 regulates cisplatin uptake in Saccharomyces cerevisiae [J]. Mol Pharmacol , 2002 , 62 ( 5 ): 1154 - 1159 . doi: 10.1124/mol.62.5.1154 http://dx.doi.org/10.1124/mol.62.5.1154 .
Martinho N , Marques JMT , Todoriko I , et al . Effect of cisplatin and its cationic analogues in the phase behavior and permeability of model lipid bilayers [J]. Mol Pharm , 2023 , 20 ( 2 ): 918 - 928 . doi: 10.1021/acs.molpharmaceut.2c00321 http://dx.doi.org/10.1021/acs.molpharmaceut.2c00321 .
Ishida S , McCormick F , Smith-McCune K , et al . Enhancing tumor-specific uptake of the anticancer drug cisplatin with a copper chelator [J]. Cancer Cell , 2010 , 17 ( 6 ): 574 - 583 . doi: 10.1016/j.ccr.2010.04.011 http://dx.doi.org/10.1016/j.ccr.2010.04.011 .
Ohrvik H , Logeman B , Turk B , et al . Cathepsin protease controls copper and cisplatin accumulation via cleavage of the Ctr1 metal-binding ectodomain [J]. J Biol Chem , 2016 , 291 ( 27 ): 13905 - 13916 . doi: 10.1074/jbc.M116.731281 http://dx.doi.org/10.1074/jbc.M116.731281 .
Yi L , Kaler S . ATP7A trafficking and mechanisms underlying the distal motor neuropathy induced by mutations in ATP7A [J]. Ann N Y Acad Sci , 2014 , 1314 ( 1 ): 49 - 54 . doi: 10.1111/nyas.12427 http://dx.doi.org/10.1111/nyas.12427 .
Tadini-Buoninsegni F , Smeazzetto S . Mechanisms of charge transfer in human copper ATPases ATP7A and ATP7B [J]. IUBMB Life , 2017 , 69 ( 4 ): 218 - 225 . doi: 10.1002/iub.1603 http://dx.doi.org/10.1002/iub.1603 .
Li YQ , Yin JY , Liu ZQ , et al . Copper efflux transporters ATP7A and ATP7B:novel biomarkers for platinum drug resistance and targets for therapy [J]. IUBMB Life , 2018 , 70 ( 3 ): 183 - 191 . doi: 10.1002/iub.1722 http://dx.doi.org/10.1002/iub.1722 .
Dolgova NV , Olson D , Lutsenko S , et al . The soluble metal-binding domain of the copper transporter ATP7B binds and detoxifies cisplatin [J]. Biochem J , 2009 , 419 ( 1 ): 51 - 56 . doi: 10.1042/BJ20081359 http://dx.doi.org/10.1042/BJ20081359 .
Samimi G , Safaei R , Katano K , et al . Increased expression of the copper efflux transporter ATP7A mediates resistance to cisplatin,carboplatin,and oxaliplatin in ovarian cancer cells [J]. Clin Cancer Res , 2004 , 10 ( 14 ): 4661 - 4669 . doi: 10.1158/1078-0432.CCR-04-0137 http://dx.doi.org/10.1158/1078-0432.CCR-04-0137 .
Mangala LS , Zuzel V , Schmandt R , et al . Therapeutic targeting of ATP7B in ovarian carcinoma [J]. Clin Cancer Res , 2009 , 15 ( 11 ): 3770 - 3780 . doi: 10.1158/1078-0432.CCR-08-2306 http://dx.doi.org/10.1158/1078-0432.CCR-08-2306 .
Nakayama K , Kanzaki A , Terada K , et al . Prognostic value of the Cu-transporting ATPase in ovarian carcinoma patients receiving cisplatin-based chemotherapy [J]. Clin Cancer Res , 2004 , 10 ( 8 ): 2804 - 2811 . doi: 10.1158/1078-0432.ccr-03-0454 http://dx.doi.org/10.1158/1078-0432.ccr-03-0454 .
Nie X , Chen H , Xiong Y , et al . Anisomycin has a potential toxicity of promoting cuproptosis in human ovarian cancer stem cells by attenuating YY1/lipoic acid pathway activation [J]. J Cancer , 2022 , 13 ( 14 ): 3503 - 3514 . doi: 10.7150/jca.77445 http://dx.doi.org/10.7150/jca.77445 .
Ewen KM , Ringle M , Bernhardt R . Adrenodoxin:a versatile ferredoxin [J]. IUBMB Life , 2012 , 64 ( 6 ): 506 - 512 . doi: 10.1002/iub.1029 http://dx.doi.org/10.1002/iub.1029 .
Dreishpoon MB , Bick NR , Petrova B , et al . FDX1 regulates cellular protein lipoylation through direct binding to LIAS [J]. J Biol Chem , 2023 , 299 ( 9 ): 105046 . doi: 10.1016/j.jbc.2023.105046 http://dx.doi.org/10.1016/j.jbc.2023.105046 .
Yoneyama K , Kojima S , Kodani Y , et al . Proteomic identification of autoantibodies in sera from patients with ovarian cancer as possible diagnostic biomarkers [J]. Anticancer Res , 2015 , 35 ( 2 ): 881 - 889 .
Dayan A , Fleminger G , Ashur-Fabian O . Targeting the Achilles' heel of cancer cells via integrin-mediated delivery of ROS-generating dihydrolipoamide dehydrogenase [J]. Oncogene , 2019 , 38 ( 25 ): 5050 - 5061 . doi: 10.1038/s41388-019-0775-9 http://dx.doi.org/10.1038/s41388-019-0775-9 .
Xie J , Yang Y , Gao Y , et al . Cuproptosis:mechanisms and links with cancers [J]. Mol Cancer , 2023 , 22 ( 1 ): 46 . doi: 10.1186/s12943-023-01732-y http://dx.doi.org/10.1186/s12943-023-01732-y .
Zhang J , Lu M , Xu H , et al . Molecular subtypes based on cuproptosis-related genes and tumor microenvironment infiltration characterization in ovarian cancer [J]. Cancer Cell Int , 2022 , 22 ( 1 ): 328 . doi: 10.1186/s12935-022-02756-y http://dx.doi.org/10.1186/s12935-022-02756-y .
Cai Y , He Q , Liu W , et al . Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers [J]. Front Oncol , 2022 , 12 : 952129 . doi: 10.3389/fonc.2022.952129 http://dx.doi.org/10.3389/fonc.2022.952129 .
Wang Y , Liang Q , Xu L , et al . Cuproptosis-related lncRNAs ovarian cancer:multi-omics analysis of molecular mechanisms and potential therapeutic targets [J]. Environ Toxicol , 2024 , 39 ( 3 ): 1650 - 1665 . doi: 10.1002/tox.24067 http://dx.doi.org/10.1002/tox.24067 .
Jimenez-Sanchez A , Cybulska P , Mager KL , et al . Unraveling tumor-immune heterogeneity in advanced ovarian cancer uncovers immunogenic effect of chemotherapy [J]. Nat Genet , 2020 , 52 ( 6 ): 582 - 593 . doi: 10.1038/s41588-020-0630-5 http://dx.doi.org/10.1038/s41588-020-0630-5 .
Arneth B . Tumor microenvironment [J]. Medicina (Kaunas) , 2019 , 56 ( 1 ): 15 . doi: 10.3390/medicina56010015 http://dx.doi.org/10.3390/medicina56010015 .
Bruni D , Angell HK , Galon J . The immune contexture and immuno-score in cancer prognosis and therapeutic efficacy [J]. Nat Rev Cancer , 2020 , 20 ( 11 ): 662 - 680 . doi: 10.1038/s41568-020-0285-7 http://dx.doi.org/10.1038/s41568-020-0285-7 .
Liu L , Wang Q , Zhou JY , et al . Developing four cuproptosis-related lncRNAs signature to predict prognosis and immune activity in ovarian cancer [J]. J Ovarian Res , 2023 , 16 ( 1 ): 88 . doi: 10.1186/s13048-023-01165-7 http://dx.doi.org/10.1186/s13048-023-01165-7 .
Goschl L , Scheinecker C , Bonelli M . Treg cells in autoimmunity:from identification to Treg-based therapies [J]. Semin Immunopathol , 2019 , 41 ( 3 ): 301 - 314 . doi: 10.1007/s00281-019-00741-8 http://dx.doi.org/10.1007/s00281-019-00741-8 .
Matulonis UA , Shapira-Frommer R , Santin AD , et al . Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer:results from the phase Ⅱ KEYNOTE-100 study [J]. Ann Oncol , 2019 , 30 ( 7 ): 1080 - 1087 . doi: 10.1093/annonc/mdz135 http://dx.doi.org/10.1093/annonc/mdz135 .
Zhang Y , Zheng J . Functions of immune checkpoint molecules beyond immune evasion [J]. Adv Exp Med Biol , 2020 , 1248 : 201 - 226 . doi: 10.1007/978-981-15-3266-5_9 http://dx.doi.org/10.1007/978-981-15-3266-5_9 .
O'Day SJ , Eggermont AM , Chiarion-Sileni V , et al . Final results of phase Ⅲ SYMMETRY study:randomized,double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma [J]. J Clin Oncol , 2013 , 31 ( 9 ): 1211 - 1218 . doi: 10.1200/JCO.2012.44.5585 http://dx.doi.org/10.1200/JCO.2012.44.5585 .
Xu Y , Liu SY , Zeng L , et al . An enzyme-engineered nonporous copper(Ⅰ) coordination polymer nanoplatform for cuproptosis-based synergistic cancer therapy [J]. Adv Mater , 2022 , 34 ( 43 ): e2204733 . doi: 10.1002/adma.202204733 http://dx.doi.org/10.1002/adma.202204733 .
Wang X , Chen D , Shi Y , et al . Copper and cuproptosis-related genes in hepatocellular carcinoma:therapeutic biomarkers targeting tumor immune microenvironment and immune checkpoints [J]. Front Immunol , 2023 , 14 : 1123231 . doi: 10.3389/fimmu.2023.1123231 http://dx.doi.org/10.3389/fimmu.2023.1123231 .
Bao JH , Lu WC , Duan H , et al . Identification of a novel cuproptosis-related gene signature and integrative analyses in patients with lower-grade gliomas [J]. Front Immunol , 2022 , 13 : 933973 . doi: 10.3389/fimmu.2022.933973 http://dx.doi.org/10.3389/fimmu.2022.933973 .
Zhou Z , Deng J , Pan T , et al . Prognostic significance of cuproptosis-related gene signatures in breast cancer based on transcriptomic data analysis [J]. Cancers (Basel) , 2022 , 14 ( 23 ): 5771 . doi: 10.3390/cancers14235771 http://dx.doi.org/10.3390/cancers14235771 .
Chen Y , Tang L , Huang W , et al . Identification of a prognostic cuproptosis-related signature in hepatocellular carcinoma [J]. Biol Direct , 2023 , 18 ( 1 ): 4 . doi: 10.1186/s13062-023-00358-w http://dx.doi.org/10.1186/s13062-023-00358-w .
Goel S , Chen F , Cai W . Synthesis and biomedical applications of copper sulfide nanoparticles:from sensors to theranostics [J]. Small , 2014 , 10 ( 4 ): 631 - 645 . doi: 10.1002/smll.201301174 http://dx.doi.org/10.1002/smll.201301174 .
Oliveri V . Selective targeting of cancer cells by copper ionophores:an overview [J]. Front Mol Biosci , 2022 , 9 : 841814 . doi: 10.3389/fmolb. 2022.841814 http://dx.doi.org/10.3389/fmolb.2022.841814 .
McMahon A , Chen W , Li F . Old wine in new bottles:advanced drug delivery systems for disulfiram-based cancer therapy [J]. J Control Release , 2020 , 319 : 352 - 359 . doi: 10.1016/j.jconrel.2020.01.001 http://dx.doi.org/10.1016/j.jconrel.2020.01.001 .
Guo F , Yang Z , Kulbe H , et al . Inhibitory effect on ovarian cancer ALDH+ stem-like cells by disulfiram and Copper treatment through ALDH and ROS modulation [J]. Biomed Pharmacother , 2019 , 118 : 109371 . doi: 10.1016/j.biopha.2019.109371 http://dx.doi.org/10.1016/j.biopha.2019.109371 .
Bair JS , Palchaudhuri R , Hergenrother PJ . Chemistry and biology of deoxynyboquinone,a potent inducer of cancer cell death [J]. J Am Chem Soc , 2010 , 132 ( 15 ): 5469 - 5478 . doi: 10.1021/ja100610m http://dx.doi.org/10.1021/ja100610m .
Kirshner JR , He S , Balasubramanyam V , et al . Elesclomol induces cancer cell apoptosis through oxidative stress [J]. Mol Cancer Ther , 2008 , 7 ( 8 ): 2319 - 2327 . doi: 10.1158/1535-7163.MCT-08-0298 http://dx.doi.org/10.1158/1535-7163.MCT-08-0298 .
Nagai M , Vo NH , Shin Ogawa L , et al . The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells [J]. Free Radic Biol Med , 2012 , 52 ( 10 ): 2142 - 2150 . doi: 10.1016/j.freeradbiomed.2012.03.017 http://dx.doi.org/10.1016/j.freeradbiomed.2012.03.017 .
Harrington BS , Ozaki MK , Caminear MW , et al . Drugs targeting tumor-initiating cells prolong survival in a post-surgery,post-chemotherapy ovarian cancer relapse model [J]. Cancers (Basel) , 2020 , 12 ( 6 ): 1645 . doi: 10.3390/cancers12061645 http://dx.doi.org/10.3390/cancers12061645 .
Monk BJ , Kauderer JT , Moxley KM , et al . A phase Ⅱ evaluation of elesclomol sodium and weekly paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian,fallopian tube or primary peritoneal cancer:an NRG oncology/gynecologic oncology group study [J]. Gynecol Oncol , 2018 , 151 ( 3 ): 422 - 427 . doi: 10.1016/j.ygyno. 2018.10.001 http://dx.doi.org/10.1016/j.ygyno.2018.10.001 .
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