{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T09:54:25Z","timestamp":1781776465915,"version":"3.54.5"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Key Projects of Shaoxing Science and Technology Plan","award":["No.2024A14010, No.2024A14015"],"award-info":[{"award-number":["No.2024A14010, No.2024A14015"]}]},{"name":"Zhejiang Provincial Health andMedicine Technology PlanningProject","award":["No.2025HY1323"],"award-info":[{"award-number":["No.2025HY1323"]}]},{"name":"Health Science and Technology Program Project from Shaoxing","award":["No.2024SKY073, No.2023SKY082"],"award-info":[{"award-number":["No.2024SKY073, No.2023SKY082"]}]},{"name":"Zhejiang Provincial Health and Medicine Technology Planning Project","award":["No.2025HY1323"],"award-info":[{"award-number":["No.2025HY1323"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Cell Biochem"],"DOI":"10.1007\/s11010-026-05556-4","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:50:30Z","timestamp":1777373430000},"page":"2593-2606","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Squalene attenuates doxorubicin resistance in hepatocellular carcinoma by targeting SIRT6 to inhibit ERK1 deacetylation"],"prefix":"10.1007","volume":"481","author":[{"given":"Geqiong","family":"Xiao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benzhen","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuemei","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"5556_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A (2024) Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 74:229\u2013263. https:\/\/doi.org\/10.3322\/caac.21834","journal-title":"CA Cancer J Clin"},{"key":"5556_CR2","doi-asserted-by":"publisher","unstructured":"De Siervi S, Turato C (2023) Liver organoids as an in vitro model to study primary liver cancer. Int J Mol Sci 24. https:\/\/doi.org\/10.3390\/ijms24054529","DOI":"10.3390\/ijms24054529"},{"key":"5556_CR3","doi-asserted-by":"publisher","unstructured":"Blidisel A, Marcovici I, Coricovac D, Hut F, Dehelean CA, Cretu OM (2021) Experimental models of hepatocellular carcinoma-a preclinical perspective. Cancers (Basel) 13. https:\/\/doi.org\/10.3390\/cancers13153651","DOI":"10.3390\/cancers13153651"},{"key":"5556_CR4","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.3748\/wjg.v29.i6.1054","volume":"29","author":"DS Mandlik","year":"2023","unstructured":"Mandlik DS, Mandlik SK, Choudhary HB (2023) Immunotherapy for hepatocellular carcinoma: current status and future perspectives. World J Gastroenterol 29:1054\u20131075. https:\/\/doi.org\/10.3748\/wjg.v29.i6.1054","journal-title":"World J Gastroenterol"},{"key":"5556_CR5","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s43556-024-00184-0","volume":"5","author":"Y Xue","year":"2024","unstructured":"Xue Y, Ruan Y, Wang Y, Xiao P, Xu J (2024) Signaling pathways in liver cancer: pathogenesis and targeted therapy. Mol Biomed 5:20. https:\/\/doi.org\/10.1186\/s43556-024-00184-0","journal-title":"Mol Biomed"},{"key":"5556_CR6","doi-asserted-by":"publisher","first-page":"101084","DOI":"10.1016\/j.drup.2024.101084","volume":"74","author":"H Zhao","year":"2024","unstructured":"Zhao H, Ling Y, He J, Dong J, Mo Q, Wang Y, Zhang Y, Yu H, Tang C (2024) Potential targets and therapeutics for cancer stem cell-based therapy against drug resistance in hepatocellular carcinoma. Drug Resist Updat 74:101084. https:\/\/doi.org\/10.1016\/j.drup.2024.101084","journal-title":"Drug Resist Updat"},{"key":"5556_CR7","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.14336\/AD.2022.0413","volume":"13","author":"Z Guo","year":"2022","unstructured":"Guo Z, Li P, Ge J, Li H (2022) SIRT6 in aging, metabolism, inflammation and cardiovascular diseases. Aging Dis 13:1787\u20131822. https:\/\/doi.org\/10.14336\/AD.2022.0413","journal-title":"Aging Dis"},{"key":"5556_CR8","doi-asserted-by":"publisher","first-page":"6526","DOI":"10.7150\/thno.53886","volume":"11","author":"Q Han","year":"2021","unstructured":"Han Q, Xie QR, Li F, Cheng Y, Wu T, Zhang Y, Lu X, Wong AST, Sha J, Xia W (2021) Targeted inhibition of SIRT6 via engineered exosomes impairs tumorigenesis and metastasis in prostate cancer. Theranostics 11:6526\u20136541. https:\/\/doi.org\/10.7150\/thno.53886","journal-title":"Theranostics"},{"key":"5556_CR9","doi-asserted-by":"publisher","first-page":"22000","DOI":"10.1038\/s41598-023-49199-7","volume":"13","author":"C Andreani","year":"2023","unstructured":"Andreani C, Bartolacci C, Persico G, Casciaro F, Amatori S, Fanelli M, Giorgio M, Galie M, Tomassoni D, Wang J, Zhang X, Bick G, Coppari R, Marchini C, Amici A (2023) SIRT6 promotes metastasis and relapse in HER2-positive breast cancer. Sci Rep 13:22000. https:\/\/doi.org\/10.1038\/s41598-023-49199-7","journal-title":"Sci Rep"},{"key":"5556_CR10","doi-asserted-by":"publisher","first-page":"2267","DOI":"10.1158\/1541-7786.MCR-19-0321","volume":"17","author":"LL Han","year":"2019","unstructured":"Han LL, Jia L, Wu F, Huang C (2019) Sirtuin6 (SIRT6) Promotes the EMT of hepatocellular carcinoma by stimulating autophagic degradation of E-Cadherin. Mol Cancer Res 17:2267\u20132280. https:\/\/doi.org\/10.1158\/1541-7786.MCR-19-0321","journal-title":"Mol Cancer Res"},{"key":"5556_CR11","doi-asserted-by":"publisher","first-page":"e70089","DOI":"10.1002\/ddr.70089","volume":"86","author":"Y Huang","year":"2025","unstructured":"Huang Y, Huang S, Li Q, Zhang H, Xiao W, Chen Y (2025) miR-338-3p targets sIRT6 to inhibit liver cancer malignancy and paclitaxel resistance. Drug Dev Res 86:e70089. https:\/\/doi.org\/10.1002\/ddr.70089","journal-title":"Drug Dev Res"},{"key":"5556_CR12","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1186\/s13046-020-01759-9","volume":"39","author":"Z Zhang","year":"2020","unstructured":"Zhang Z, Ha SH, Moon YJ, Hussein UK, Song Y, Kim KM, Park SH, Park HS, Park BH, Ahn AR, Lee SA, Ahn SJ, Kim JR, Jang KY (2020) Inhibition of SIRT6 potentiates the anti-tumor effect of doxorubicin through suppression of the DNA damage repair pathway in osteosarcoma. J Exp Clin Cancer Res 39:247. https:\/\/doi.org\/10.1186\/s13046-020-01759-9","journal-title":"J Exp Clin Cancer Res"},{"key":"5556_CR13","doi-asserted-by":"publisher","unstructured":"Micera M, Botto A, Geddo F, Antoniotti S, Bertea CM, Levi R, Gallo MP, Querio G (2020) Squalene: more than a step toward sterols. Antioxid (Basel) 9. https:\/\/doi.org\/10.3390\/antiox9080688","DOI":"10.3390\/antiox9080688"},{"key":"5556_CR14","doi-asserted-by":"publisher","unstructured":"Bidooki SH, Quero J, Sanchez-Marco J, Herrero-Continente T, Marmol I, Lasheras R, Sebastian V, Arruebo M, Osada J, Rodriguez-Yoldi MJ (2024) Squalene in nanoparticles improves antiproliferative effect on human colon carcinoma cells through apoptosis by disturbances in redox balance. Int J Mol Sci 25. https:\/\/doi.org\/10.3390\/ijms252313048","DOI":"10.3390\/ijms252313048"},{"key":"5556_CR15","doi-asserted-by":"publisher","unstructured":"Bidooki SH, Alejo T, Sanchez-Marco J, Martinez-Beamonte R, Abuobeid R, Burillo JC, Lasheras R, Sebastian V, Rodriguez-Yoldi MJ, Arruebo M, Osada J (2022) Squalene loaded nanoparticles effectively protect hepatic AML12 cell lines against oxidative and endoplasmic reticulum stress in a TXNDC5-dependent way. Antioxid (Basel) 11. https:\/\/doi.org\/10.3390\/antiox11030581","DOI":"10.3390\/antiox11030581"},{"key":"5556_CR16","doi-asserted-by":"publisher","unstructured":"Sanchez-Quesada C, Gutierrez-Santiago F, Rodriguez-Garcia C, Gaforio JJ (2022) Synergistic effect of squalene and hydroxytyrosol on highly invasive MDA-MB-231 breast cancer cells. Nutrients 14. https:\/\/doi.org\/10.3390\/nu14020255","DOI":"10.3390\/nu14020255"},{"key":"5556_CR17","doi-asserted-by":"publisher","unstructured":"Feng J, Wen C, Zhang X, Zhu X, Ma M, Zhao X, Sui X (2025) A novel squalenoylated temozolomide nanoparticle with long circulating properties reverses drug resistance in glioblastoma. Int J Mol Sci 26. https:\/\/doi.org\/10.3390\/ijms26104723","DOI":"10.3390\/ijms26104723"},{"key":"5556_CR18","doi-asserted-by":"publisher","first-page":"2104","DOI":"10.1111\/cns.13945","volume":"28","author":"L Yao","year":"2022","unstructured":"Yao L, Li J, Zhang X, Zhou L, Hu K (2022) Downregulated ferroptosis-related gene SQLE facilitates temozolomide chemoresistance, and invasion and affects immune regulation in glioblastoma. CNS Neurosci Ther 28:2104\u20132115. https:\/\/doi.org\/10.1111\/cns.13945","journal-title":"CNS Neurosci Ther"},{"key":"5556_CR19","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.3892\/mmr.2019.10398","volume":"20","author":"C Zhang","year":"2019","unstructured":"Zhang C, Yu Y, Huang Q, Tang K (2019) SIRT6 regulates the proliferation and apoptosis of hepatocellular carcinoma via the ERK1\/2 signaling pathway. Mol Med Rep 20:1575\u20131582. https:\/\/doi.org\/10.3892\/mmr.2019.10398","journal-title":"Mol Med Rep"},{"key":"5556_CR20","doi-asserted-by":"publisher","first-page":"103407","DOI":"10.1016\/j.redox.2024.103407","volume":"77","author":"J Zhang","year":"2024","unstructured":"Zhang J, Xu H, He Y, Zheng X, Lin T, Yang L, Tan P, Wei Q (2024) Inhibition of KDM4A restricts SQLE transcription and induces oxidative stress imbalance to suppress bladder cancer. Redox Biol 77:103407. https:\/\/doi.org\/10.1016\/j.redox.2024.103407","journal-title":"Redox Biol"},{"key":"5556_CR21","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1074\/jbc.M117.795955","volume":"293","author":"JY Wu","year":"2018","unstructured":"Wu JY, Xiang S, Zhang M, Fang B, Huang H, Kwon OK, Zhao Y, Yang Z, Bai W, Bepler G, Zhang XM (2018) Histone deacetylase 6 (HDAC6) deacetylates extracellular signal-regulated kinase 1 (ERK1) and thereby stimulates ERK1 activity. J Biol Chem 293:1976\u20131993. https:\/\/doi.org\/10.1074\/jbc.M117.795955","journal-title":"J Biol Chem"},{"key":"5556_CR22","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1080\/13880209.2020.1742167","volume":"58","author":"L Yang","year":"2020","unstructured":"Yang L, Zhang C, Chen J, Zhang S, Pan G, Xin Y, Lin L, You Z (2020) Shenmai injection suppresses multidrug resistance in MCF-7\/ADR cells through the MAPK\/NF-kappaB signalling pathway. Pharm Biol 58:276\u2013285. https:\/\/doi.org\/10.1080\/13880209.2020.1742167","journal-title":"Pharm Biol"},{"key":"5556_CR23","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/s41392-020-00264-x","volume":"5","author":"A Huang","year":"2020","unstructured":"Huang A, Yang XR, Chung WY, Dennison AR, Zhou J (2020) Targeted therapy for hepatocellular carcinoma. Signal Transduct Target Ther 5:146. https:\/\/doi.org\/10.1038\/s41392-020-00264-x","journal-title":"Signal Transduct Target Ther"},{"key":"5556_CR24","doi-asserted-by":"publisher","first-page":"101205","DOI":"10.1016\/j.mam.2023.101205","volume":"93","author":"R Mattioli","year":"2023","unstructured":"Mattioli R, Ilari A, Colotti B, Mosca L, Fazi F, Colotti G (2023) Doxorubicin and other anthracyclines in cancers: activity, chemoresistance and its overcoming. Mol Aspects Med 93:101205. https:\/\/doi.org\/10.1016\/j.mam.2023.101205","journal-title":"Mol Aspects Med"},{"key":"5556_CR25","doi-asserted-by":"publisher","unstructured":"Huang PS, Wang LY, Wang YW, Tsai MM, Lin TK, Liao CJ, Yeh CT, Lin KH (2023) Evaluation and application of drug resistance by biomarkers in the clinical treatment of liver cancer. Cells 12. https:\/\/doi.org\/10.3390\/cells12060869","DOI":"10.3390\/cells12060869"},{"key":"5556_CR26","doi-asserted-by":"publisher","first-page":"119527","DOI":"10.1016\/j.lfs.2021.119527","volume":"278","author":"S Sritharan","year":"2021","unstructured":"Sritharan S, Sivalingam N (2021) A comprehensive review on time-tested anticancer drug doxorubicin. Life Sci 278:119527. https:\/\/doi.org\/10.1016\/j.lfs.2021.119527","journal-title":"Life Sci"},{"key":"5556_CR27","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1007\/s00280-021-04238-w","volume":"87","author":"X Yi","year":"2021","unstructured":"Yi X, Lou L, Wang J, Xiong J, Zhou S (2021) Honokiol antagonizes doxorubicin resistance in human breast cancer via miR-188-5p\/FBXW7\/c-Myc pathway. Cancer Chemother Pharmacol 87:647\u2013656. https:\/\/doi.org\/10.1007\/s00280-021-04238-w","journal-title":"Cancer Chemother Pharmacol"},{"key":"5556_CR28","doi-asserted-by":"publisher","first-page":"e14587","DOI":"10.1111\/cbdd.14587","volume":"104","author":"M Shimia","year":"2024","unstructured":"Shimia M, Amini M, Ravari AO, Tabnak P, Valizadeh A, Ghaheri M, Yousefi B (2024) Thymoquinone reversed doxorubicin resistance in U87 glioblastoma cells via targeting PI3K\/Akt\/mTOR signaling. Chem Biol Drug Des 104:e14587. https:\/\/doi.org\/10.1111\/cbdd.14587","journal-title":"Chem Biol Drug Des"},{"key":"5556_CR29","doi-asserted-by":"publisher","first-page":"552088","DOI":"10.3389\/fphar.2020.552088","volume":"11","author":"M Vagvolgyi","year":"2020","unstructured":"Vagvolgyi M, Belteky P, Bogdan D, Nove M, Spengler G, Latif AD, Zupko I, Gati T, Toth G, Konya Z, Hunyadi A (2020) Squalenoylated nanoparticle pro-drugs of adjuvant antitumor 11alpha-hydroxyecdysteroid 2,3-acetonides act as cytoprotective agents against doxorubicin and paclitaxel. Front Pharmacol 11:552088. https:\/\/doi.org\/10.3389\/fphar.2020.552088","journal-title":"Front Pharmacol"},{"key":"5556_CR30","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s13046-020-01623-w","volume":"39","author":"J Yang","year":"2020","unstructured":"Yang J, Li Y, Zhang Y, Fang X, Chen N, Zhou X, Wang X (2020) Sirt6 promotes tumorigenesis and drug resistance of diffuse large B-cell lymphoma by mediating PI3K\/Akt signaling. J Exp Clin Cancer Res 39:142. https:\/\/doi.org\/10.1186\/s13046-020-01623-w","journal-title":"J Exp Clin Cancer Res"},{"key":"5556_CR31","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3389\/fphar.2018.00194","volume":"9","author":"YQ Xia","year":"2018","unstructured":"Xia YQ, Hua RJ, Juan C, Zhong ZH, Tao CS, Fang R, Lin H, Rui G, Yong C (2018) SIRT6 depletion sensitizes human hepatoma cells to chemotherapeutics by downregulating MDR1 expression. Front Pharmacol 9:194. https:\/\/doi.org\/10.3389\/fphar.2018.00194","journal-title":"Front Pharmacol"},{"key":"5556_CR32","doi-asserted-by":"publisher","unstructured":"Sugiura R, Satoh R, Takasaki T (2021) ERK: a double-edged sword in cancer. ERK-dependent apoptosis as a potential therapeutic strategy for cancer. Cells 10. https:\/\/doi.org\/10.3390\/cells10102509","DOI":"10.3390\/cells10102509"},{"key":"5556_CR33","doi-asserted-by":"publisher","first-page":"2403","DOI":"10.7150\/ijbs.87442","volume":"20","author":"Y He","year":"2024","unstructured":"He Y, Zhang X, Pan W, Zhang J, Zhu W, Zhang J, Shi J (2024) Ciliogenesis-associated kinase 1 promotes breast cancer cell proliferation and chemoresistance via phosphorylating ERK1. Int J Biol Sci 20:2403\u20132421. https:\/\/doi.org\/10.7150\/ijbs.87442","journal-title":"Int J Biol Sci"},{"key":"5556_CR34","doi-asserted-by":"publisher","first-page":"519","DOI":"10.3892\/ol.2023.14106","volume":"26","author":"X Lin","year":"2023","unstructured":"Lin X, He J, Liu F, Li L, Sun L, Niu L, Xi H, Zhan Y, Liu X, Hu P (2023) beta\u2013adrenergic receptor activation promotes the proliferation of HepG2 cells via the ERK1\/2\/CREB pathways. Oncol Lett 26:519. https:\/\/doi.org\/10.3892\/ol.2023.14106","journal-title":"Oncol Lett"}],"container-title":["Molecular and Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-026-05556-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11010-026-05556-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11010-026-05556-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T09:02:16Z","timestamp":1781773336000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11010-026-05556-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["5556"],"URL":"https:\/\/doi.org\/10.1007\/s11010-026-05556-4","relation":{},"ISSN":["1573-4919"],"issn-type":[{"value":"1573-4919","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]},"assertion":[{"value":"9 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Experiments were approved by the ethics committee of Hangzhou City University, in compliance with institutional guidelines for the care and use of animals, Approval number 25086.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}