{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:07:26Z","timestamp":1790352446585,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,5,19]],"date-time":"2024-05-19T00:00:00Z","timestamp":1716076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hepatocellular carcinoma (HCC) is one of the deadliest cancers. The prevention and therapy for this deadly disease remain a global medical challenge. In this study, we investigated the effect of pantoprazole (PPZ) on the carcinogenesis and growth of HCC. Both diethylnitrosamine (DEN) plus CCl4\u2010induced and DEN plus high fat diet (HFD)\u2010induced HCC models in mice were established. Cytokines and cell proliferation\u2010associated gene in the liver tissues of mice and HCC cells were analyzed. Cellular glycolysis and Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchange activity were measured. The preventive administration of pantoprazole (PPZ) at a clinically relevant low dose markedly suppressed HCC carcinogenesis in both DEN plus CCl4\u2010induced and HFD\u2010induced murine HCC models, whereas the therapeutic administration of PPZ at the dose suppressed the growth of HCC. In the liver tissues of PPZ\u2010treated mice, inflammatory cytokines, IL1, CXCL1, CXCL5, CXCL9, CXCL10, CCL2, CCL5, CCL6, CCL7, CCL20, and CCL22, were reduced. The administration of CXCL1, CXCL5, CCL2, or CCL20 all reversed PPZ\u2010suppressed DEN plus CCL4\u2010induced HCC carcinogenesis in mice. PPZ inhibited the expressions of CCNA2, CCNB2, CCNE2, CDC25C, CDCA5, CDK1, CDK2, TOP2A, TTK, AURKA, and BIRC5 in HCC cells. Further results showed that PPZ reduced the production of these inflammatory cytokines and the expression of these cell proliferation\u2010associated genes through the inhibition of glycolysis and Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchange. In conclusion, PPZ suppresses the carcinogenesis and growth of HCC, which is related to inhibiting the production of inflammatory cytokines and the expression of cell proliferation\u2010associated genes in the liver through the inhibition of glycolysis and Na<jats:sup>+<\/jats:sup>\/H<jats:sup>+<\/jats:sup> exchange.<\/jats:p>","DOI":"10.1002\/ddr.22198","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:55:20Z","timestamp":1716166520000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pantoprazole suppresses carcinogenesis and growth of hepatocellular carcinoma by inhibiting glycolysis and Na<sup>+<\/sup>\/H<sup>+<\/sup> exchange"],"prefix":"10.1002","volume":"85","author":[{"given":"Hai","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Digestive Disease Hospital Affiliated Hospital of Zunyi Medical University  Zunyi 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