{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:40:40Z","timestamp":1785796840705,"version":"3.56.0"},"reference-count":38,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology in Vitro"],"published-print":{"date-parts":[[2021,10]]},"DOI":"10.1016\/j.tiv.2021.105226","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T01:46:45Z","timestamp":1626745605000},"page":"105226","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Increased effects of 2,5-dimethylcelecoxib on sensitivity of hepatocellular carcinoma cells to sorafenib via CYP3A5 expression and activation of AMPK"],"prefix":"10.1016","volume":"76","author":[{"given":"Yiyin","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banglun","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanfei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanhong","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.tiv.2021.105226_bb0005","doi-asserted-by":"crossref","first-page":"87684","DOI":"10.18632\/oncotarget.21196","article-title":"Capsaicin exerts synergistic antitumor effect with sorafenib in hepatocellular carcinoma cells through AMPK activation","volume":"8","author":"Bort","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.tiv.2021.105226_bb0010","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1002\/1878-0261.12488","article-title":"Targeting AMP-activated kinase impacts hepatocellular cancer stem cells induced by long-term treatment with sorafenib","volume":"13","author":"Bort","year":"2019","journal-title":"Mol. Oncol."},{"key":"10.1016\/j.tiv.2021.105226_bb0015","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/clpt.2011.35","article-title":"Disease-drug-drug interaction involving tocilizumab and simvastatin in patients with rheumatoid arthritis","volume":"89","author":"C, S., B, K., X, Z., AJ, K., S, G","year":"2011","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.tiv.2021.105226_bb0020","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0065569","article-title":"Novel combination of sorafenib and celecoxib provides synergistic anti-proliferative and pro-apoptotic effects in human liver cancer cells","volume":"8","author":"Cervello","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.tiv.2021.105226_bb0025","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3389\/fendo.2018.00338","article-title":"PTEN: tumor suppressor and metabolic regulator","volume":"9","author":"Chen","year":"2018","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.tiv.2021.105226_bb0030","first-page":"1467","article-title":"Preventive effect of celecoxib in sorafenib-related hand-foot syndrome in hepatocellular carcinoma patients, a single-center, open-label, randomized, controlled clinical phase III trial","volume":"10","author":"Chen","year":"2020","journal-title":"Am. J. Cancer Res."},{"key":"10.1016\/j.tiv.2021.105226_bb0035","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2020-001377","article-title":"2,5-dimethylcelecoxib improves immune microenvironment of hepatocellular carcinoma by promoting ubiquitination of HBx-induced PD-L1","volume":"8","author":"Chen","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"10.1016\/j.tiv.2021.105226_bb0040","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S1470-2045(08)70285-7","article-title":"Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial","volume":"10","author":"Cheng","year":"2009","journal-title":"Lancet Oncol."},{"key":"10.1016\/j.tiv.2021.105226_bb0045","article-title":"AMP-activated protein kinase suppresses the in vitro and in vivo proliferation of hepatocellular carcinoma","volume":"9","author":"Cheng","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.tiv.2021.105226_bb0050","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","article-title":"Drug combination studies and their synergy quantification using the Chou-Talalay method","volume":"70","author":"Chou","year":"2010","journal-title":"Cancer Res."},{"key":"10.1016\/j.tiv.2021.105226_bb0055","doi-asserted-by":"crossref","first-page":"3870","DOI":"10.3748\/wjg.v25.i29.3870","article-title":"Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma","volume":"25","author":"De Mattia","year":"2019","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.tiv.2021.105226_bb0060","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1016\/j.bcp.2010.07.032","article-title":"Dimethylcelecoxib inhibits mPGES-1 promoter activity by influencing EGR1 and NF-\u03baB","volume":"80","author":"Deckmann","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.tiv.2021.105226_bb0065","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1158\/0008-5472.CAN-14-1589","article-title":"CYP3A5 functions as a tumor suppressor in hepatocellular carcinoma by regulating mTORC2\/Akt signaling","volume":"75","author":"F, J., L, C., YC, Y., XM, W., RY, W., L, L., W, W., YX, C., CY, C., J, T., GM, L., WT, H., L, X., HY, W","year":"2015","journal-title":"Cancer Res."},{"key":"10.1016\/j.tiv.2021.105226_bb0070","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.3389\/fonc.2020.01563","article-title":"Matrix stiffness-Upregulated MicroRNA-17-5p attenuates the intervention effects of metformin on HCC invasion and metastasis by targeting the PTEN\/PI3K\/Akt pathway","volume":"10","author":"Gao","year":"2020","journal-title":"Front. Oncol."},{"key":"10.1016\/j.tiv.2021.105226_bb0075","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S0140-6736(05)17864-7","article-title":"Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study","volume":"365","author":"Graham","year":"2005","journal-title":"Lancet (London, England)"},{"key":"10.1016\/j.tiv.2021.105226_bb0080","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/1878-0261.12039","article-title":"Dual inhibition of Akt and c-met as a second-line therapy following acquired resistance to sorafenib in hepatocellular carcinoma cells","volume":"11","author":"Han","year":"2017","journal-title":"Mol. Oncol."},{"key":"10.1016\/j.tiv.2021.105226_bb0085","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41392-020-00264-x","article-title":"Targeted therapy for hepatocellular carcinoma","volume":"5","author":"Huang","year":"2020","journal-title":"Sign. Transd. Target. Ther."},{"key":"10.1016\/j.tiv.2021.105226_bb0090","first-page":"11","article-title":"The role of AMP-activated protein kinase as a potential target of treatment of hepatocellular carcinoma","author":"Jiang","year":"2019","journal-title":"Cancers"},{"key":"10.1016\/j.tiv.2021.105226_bb0095","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2165\/00003495-200969020-00006","article-title":"Sorafenib: a review of its use in advanced hepatocellular carcinoma","volume":"69","author":"Keating","year":"2009","journal-title":"Drugs"},{"key":"10.1016\/j.tiv.2021.105226_bb0100","doi-asserted-by":"crossref","first-page":"899","DOI":"10.3892\/or.2017.5722","article-title":"Targeting the PD-L1\/DNMT1 axis in acquired resistance to sorafenib in human hepatocellular carcinoma","volume":"38","author":"Liu","year":"2017","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.tiv.2021.105226_bb0105","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.tiv.2021.105226_bb0110","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.bbcan.2017.10.002","article-title":"New insights into sorafenib resistance in hepatocellular carcinoma: responsible mechanisms and promising strategies","volume":"1868","author":"Niu","year":"2017","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"10.1016\/j.tiv.2021.105226_bb0115","doi-asserted-by":"crossref","first-page":"411","DOI":"10.21037\/hbsn.2019.04.01","article-title":"Sorafenib and metformin: to be, or not to be, that is the question","volume":"8","author":"Orsi","year":"2019","journal-title":"Hepatob. Surg. Nutrit."},{"key":"10.1016\/j.tiv.2021.105226_bb0120","doi-asserted-by":"crossref","first-page":"7492","DOI":"10.18632\/aging.102262","article-title":"PTEN loss regulates alveolar epithelial cell senescence in pulmonary fibrosis depending on Akt activation","volume":"11","author":"Qiu","year":"2019","journal-title":"Aging"},{"key":"10.1016\/j.tiv.2021.105226_bb0125","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/clpt.2014.143","article-title":"Cancer, inflammation, and therapy: effects on cytochrome p450-mediated drug metabolism and implications for novel immunotherapeutic agents","volume":"96","author":"RD, H., ET, M","year":"2014","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.tiv.2021.105226_bb0130","doi-asserted-by":"crossref","DOI":"10.3390\/biom10081199","article-title":"The protective role of Decorin in hepatic metastasis of colorectal carcinoma","volume":"10","author":"Reszegi","year":"2020","journal-title":"Biomolecules"},{"key":"10.1016\/j.tiv.2021.105226_bb0135","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/clpt.2009.308","article-title":"Therapeutic protein-drug interactions and implications for drug development","volume":"87","author":"SM, H., H, Z., JI, L., K, R., L, Z., R, T., LJ, L","year":"2010","journal-title":"Clin. Pharmacol. Ther."},{"key":"10.1016\/j.tiv.2021.105226_bb0140","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.canlet.2017.06.029","article-title":"Aspirin disrupts the mTOR-raptor complex and potentiates the anti-cancer activities of sorafenib via mTORC1 inhibition","volume":"406","author":"Sun","year":"2017","journal-title":"Cancer Lett."},{"key":"10.1016\/j.tiv.2021.105226_bb0145","first-page":"973","article-title":"miR-543 acts as a novel oncogene in oral squamous cell carcinoma by targeting CYP3A5","volume":"42","author":"Wang","year":"2019","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.tiv.2021.105226_bb0150","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.bcp.2008.04.008","article-title":"Dimethylcelecoxib inhibits prostaglandin E2 production","volume":"76","author":"Wobst","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.tiv.2021.105226_bb0155","doi-asserted-by":"crossref","first-page":"105195","DOI":"10.1016\/j.phrs.2020.105195","article-title":"PI3K\/AKT\/mTOR pathway-related long non-coding RNAs: roles and mechanisms in hepatocellular carcinoma","volume":"160","author":"Wu","year":"2020","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.tiv.2021.105226_bb0160","first-page":"586","article-title":"Specific CYP450 genotypes in the Chinese population affect Sorafenib toxicity in HBV\/HCV-associated hepatocellular carcinoma patients","volume":"31","author":"XG, G., ZH, W., W, D., XD, H., FC, L., H, L","year":"2018","journal-title":"Biom. Environ. Sci. BES"},{"key":"10.1016\/j.tiv.2021.105226_bb0165","doi-asserted-by":"crossref","DOI":"10.1158\/1535-7163.MCT-19-1141","article-title":"Synthetic lethal metabolic targeting of androgen deprived prostate Cancer cells with metformin","author":"Yang","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.tiv.2021.105226_bb0170","doi-asserted-by":"crossref","first-page":"179","DOI":"10.14701\/ahbps.2018.22.3.179","article-title":"In vitroSynergistic effect of metformin on sorafenib in study using hepatocellular carcinoma cell lines","volume":"22","author":"YG, C., E, T., S, H., JY, L., JY, K., YY, K., GW, S., KJ, L., N, K","year":"2018","journal-title":"Ann. Hepato-biliary-pancreatic Surg."},{"issue":"3","key":"10.1016\/j.tiv.2021.105226_bb0175","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41388-020-01545-z","article-title":"Cytochrome P450 1A2 overcomes nuclear factor kappa B-mediated sorafenib resistance in hepatocellular carcinoma","volume":"40","author":"Yu","year":"2021","journal-title":"Oncogene."},{"key":"10.1016\/j.tiv.2021.105226_bb0180","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1080\/14756366.2019.1587416","article-title":"CRISPR\/Cas9-based liver-derived reporter cells for screening of mPGES-1 inhibitors","volume":"34","author":"Z, C., X, C., M, L., L, Y., L, W., X, W., N, T","year":"2019","journal-title":"J. Enzyme Inhibit. Med. Chem."},{"key":"10.1016\/j.tiv.2021.105226_bb0185","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1159\/000488035","article-title":"Guidelines for diagnosis and treatment of primary liver Cancer in China (2017 edition)","volume":"7","author":"Zhou","year":"2018","journal-title":"Liver Cancer"},{"key":"10.1016\/j.tiv.2021.105226_bb0190","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/aps.2017.5","article-title":"New knowledge of the mechanisms of sorafenib resistance in liver cancer","volume":"38","author":"Zhu","year":"2017","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Toxicology in Vitro"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S088723332100151X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S088723332100151X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:38:03Z","timestamp":1760135883000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S088723332100151X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":38,"alternative-id":["S088723332100151X"],"URL":"https:\/\/doi.org\/10.1016\/j.tiv.2021.105226","relation":{},"ISSN":["0887-2333"],"issn-type":[{"value":"0887-2333","type":"print"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Increased effects of 2,5-dimethylcelecoxib on sensitivity of hepatocellular carcinoma cells to sorafenib via CYP3A5 expression and activation of AMPK","name":"articletitle","label":"Article Title"},{"value":"Toxicology in Vitro","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tiv.2021.105226","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"105226"}}