{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T01:04:31Z","timestamp":1768871071378,"version":"3.49.0"},"reference-count":68,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T00:00:00Z","timestamp":1718323200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parecoxib, a well\u2010recognized nonsteroidal anti\u2010inflammatory drug, has been reported to possess anticancer properties in various tumor types. In this work, we aimed to investigate the potential anticancer effects of parecoxib on hepatocellular carcinoma (HCC) cells. To assess the impact of parecoxib on HCC cell proliferation, we employed Cell Counting Kit\u20108, colony formation, and 5\u2010ethynyl\u20102\u2032\u2010deoxyuridine assays. Hoechst\/propidium iodide (PI) double staining and flow cytometry were performed to evaluate apoptosis and cell cycle analysis. Wound healing and transwell assays were utilized to assess cell migration and invasion. Tube formation assay was employed to analyze angiogenesis. Protein levels were determined using western blotting, and mRNA expression levels were assessed using quantitative real\u2010time polymerase chain reaction (PCR). A xenograft mouse model was used to confirm the antitumor effects of parecoxib on HCC tumors in vivo. Our data demonstrated that parecoxib effectively inhibited the proliferation of HCC cells in a dose\u2010 and time\u2010dependent manner. In addition, parecoxib induced cell cycle arrest in the G2 phase and promoted apoptosis. Moreover, parecoxib hindered tumor migration and invasion by impeding the epithelial\u2013mesenchymal transition process. Further investigation showed that parecoxib could significantly suppress angiogenesis through the inhibition of extracellular signal\u2010regulated kinase (ERK)\u2013vascular endothelial growth factor (VEGF) axis. Notably, treatment with the ERK activator phorbol myristate acetate upregulated the expression of matrix metalloproteinase (MMP)\u20102, MMP\u20109, and VEGF and reversed the function of parecoxib in HCC cells. Besides, parecoxib displayed its antitumor efficacy in vivo. Collectively, our results suggest that parecoxib ameliorates HCC progression by regulating proliferation, cell cycle, apoptosis, migration, invasion, and angiogenesis through the ERK\u2013VEGF\/MMPs signaling pathway.<\/jats:p>","DOI":"10.1002\/iub.2861","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T10:01:45Z","timestamp":1718359305000},"page":"972-986","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Parecoxib inhibits tumorigenesis and angiogenesis in hepatocellular carcinoma through <scp>ERK<\/scp>\u2013<scp>VEGF<\/scp>\/<scp>MMPs<\/scp> signaling pathway"],"prefix":"10.1002","volume":"76","author":[{"given":"Li","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery Guizhou Provincial People's Hospital  Guiyang Guizhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1265-8956","authenticated-orcid":false,"given":"YuQi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The First Affiliated Hospital Zhejiang University School of Medicine  Zhejiang Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Guizhou Provincial People's Hospital  Guiyang Guizhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"JiangWei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Guizhou Provincial People's Hospital  Guiyang Guizhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery Guizhou Provincial People's Hospital  Guiyang Guizhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30010-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01200-4"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.5582\/bst.2022.01109"},{"key":"e_1_2_9_6_1","article-title":"NOP2\u2010mediated m5C modification of c\u2010Myc in an EIF3A\u2010dependent manner to reprogram glucose metabolism and promote hepatocellular carcinoma progression","volume":"6","author":"Zhang H","year":"2023","journal-title":"Research (Washington, DC)"},{"key":"e_1_2_9_7_1","article-title":"Comprehensive metabolic profiling and genome\u2010wide analysis reveal therapeutic modalities for hepatocellular carcinoma","volume":"6","author":"Qi F","year":"2023","journal-title":"Research (Washington, DC)"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2766"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v13.i11.1568"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.135661"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-021-01107-w"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-023-05425-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108519"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2023.110866"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e18240"},{"key":"e_1_2_9_16_1","first-page":"671","article-title":"Sorafenib inhibits TPA\u2010induced MMP\u20109 and VEGF expression via suppression of ERK\/NF\u2010\u03baB pathway in hepatocellular carcinoma cells","volume":"26","author":"Chiang IT","year":"2012","journal-title":"In Vivo (Athens, Greece)"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.22904"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7079308"},{"key":"e_1_2_9_19_1","first-page":"252","article-title":"The protective role of etoricoxib against diethylnitrosamine\/2\u2010acetylaminofluorene\u2010induced hepatocarcinogenesis in Wistar rats: the impact of NF\u2010\u03baB\/COX\u20102\/PGE2 signaling","volume":"15","author":"Ali G","year":"2022","journal-title":"Curr Mol Pharmacol"},{"key":"e_1_2_9_20_1","first-page":"4360","article-title":"Cyclooxygenase\u20102 expressed hepatocellular carcinoma induces cytotoxic T lymphocytes exhaustion through M2 macrophage polarization","volume":"13","author":"Xun X","year":"2021","journal-title":"Am J Transl Res"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.52298"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003495-200161080-00010"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/14767058.2019.1685972"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/5123933"},{"key":"e_1_2_9_25_1","first-page":"4779","article-title":"Efficacy of intravenous perioperative parecoxib administration in the surgical fixation of unstable ankle fracture: a prospective, double\u2010blinded, randomized, placebo\u2010controlled trial","volume":"25","author":"Angthong C","year":"2021","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40122-022-00400-1"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2013.1118"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2021.09.019"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00363"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/tox.23631"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-023-10199-6"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-016-4207-8"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacr.2021.09.029"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.912843"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8560"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/jep.13256"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110393"},{"key":"e_1_2_9_38_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells10061484","article-title":"Xanthohumol impairs the PMA\u2010driven invasive behaviour of lung cancer cell line A549 and exerts anti\u2010EMT action","volume":"10","author":"S\u0142awi\u0144ska\u2010Brych A","year":"2021","journal-title":"Cells"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9512"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2022.799795"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000901"},{"key":"e_1_2_9_42_1","first-page":"311","article-title":"Parecoxib inhibits glioblastoma cell proliferation, migration and invasion by upregulating miRNA\u201029c","volume":"6","author":"Li LY","year":"2017","journal-title":"Biol Open"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.7314\/APJCP.2015.16.2.627"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01268-0"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27411"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107704"},{"key":"e_1_2_9_47_1","first-page":"370","article-title":"Nimesulide inhibits proliferation and induces apoptosis of pancreatic cancer cells by enhancing expression of PTEN","volume":"16","author":"Chu M","year":"2018","journal-title":"Exp Ther Med"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.09.059"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/35077213"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-016-0433-9"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e18127"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020117-043854"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13258-023-01445-y"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2023.08.004"},{"key":"e_1_2_9_55_1","first-page":"6562","article-title":"Exogenous hydrogen sulfide promotes hepatocellular carcinoma cell growth by activating the STAT3\u2010COX\u20102 signaling pathway","volume":"15","author":"Zhen Y","year":"2018","journal-title":"Oncol Lett"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.919218"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1615\/JEnvironPatholToxicolOncol.2021039471"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105507"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00288-4"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13046-018-0926-9"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.572861"},{"key":"e_1_2_9_62_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20092164","article-title":"ERK: a key player in the pathophysiology of cardiac hypertrophy","volume":"20","author":"Gallo S","year":"2019","journal-title":"Int J Mol Sci"},{"key":"e_1_2_9_63_1","first-page":"1997","article-title":"ERK\/MAPK signalling pathway and tumorigenesis","volume":"19","author":"Guo YJ","year":"2020","journal-title":"Exp Ther Med"},{"key":"e_1_2_9_64_1","first-page":"455","article-title":"Vascular endothelial growth factor (VEGF) \u2013 key factor in normal and pathological angiogenesis","volume":"59","author":"Melincovici CS","year":"2018","journal-title":"Rom J Morphol Embryol"},{"key":"e_1_2_9_65_1","article-title":"The role of matrix metalloproteinases in the epithelial\u2013mesenchymal transition of hepatocellular carcinoma","volume":"2019","author":"Scheau C","year":"2019","journal-title":"Anal Cell Pathol (Amst)"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2017.21.5.465"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1159\/000490394"},{"key":"e_1_2_9_68_1","first-page":"3811","article-title":"COX\u20102 promotes epithelial\u2013mesenchymal transition and migration in osteosarcoma MG\u201063 cells via PI3K\/AKT\/NF\u2010kappaB signaling","volume":"20","author":"Zhang X","year":"2019","journal-title":"Mol Med Rep"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2023.11850"}],"container-title":["IUBMB Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/iub.2861","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,15]],"date-time":"2024-10-15T13:56:30Z","timestamp":1729000590000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/iub.2861"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,14]]},"references-count":68,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11]]}},"alternative-id":["10.1002\/iub.2861"],"URL":"https:\/\/doi.org\/10.1002\/iub.2861","archive":["Portico"],"relation":{},"ISSN":["1521-6543","1521-6551"],"issn-type":[{"value":"1521-6543","type":"print"},{"value":"1521-6551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,14]]},"assertion":[{"value":"2023-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}