{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T02:26:13Z","timestamp":1783131973151,"version":"3.54.6"},"reference-count":75,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:00:00Z","timestamp":1689552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science KAKENHI Grant-in-Aid for Scientific Research","award":["19K16776"],"award-info":[{"award-number":["19K16776"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammatory processes play major roles in carcinogenesis and the progression of hepatocellular carcinoma (HCC) derived from non-alcoholic steatohepatitis (NASH). But, there are no therapies for NASH-related HCC, especially focusing on these critical steps. Previous studies have reported that farnesyltransferase inhibitors (FTIs) have anti-inflammatory and anti-tumor effects. However, the influence of FTIs on NASH-related HCC has not been elucidated. In hepatoblastoma and HCC cell lines, HepG2, Hep3B, and Huh-7, we confirmed the expression of hypoxia-inducible factor (HIF)-1\u03b1, an accelerator of tumor aggressiveness and the inflammatory response. We established NASH-related HCC models under inflammation and free fatty acid burden and confirmed that HIF-1\u03b1 expression was increased under both conditions. Tipifarnib, which is an FTI, strongly suppressed increased HIF-1\u03b1, inhibited cell proliferation, and induced apoptosis. Simultaneously, intracellular interleukin-6 as an inflammation marker was increased under both conditions and significantly suppressed by tipifarnib. Additionally, tipifarnib suppressed the expression of phosphorylated nuclear factor-\u03baB and transforming growth factor-\u03b2. Finally, in a NASH-related HCC mouse model burdened with diethylnitrosamine and a high-fat diet, tipifarnib significantly reduced tumor nodule formation in association with decreased serum interleukin-6. In conclusion, tipifarnib has anti-tumor and anti-inflammatory effects in a NASH-related HCC model and may be a promising new agent to treat this disease.<\/jats:p>","DOI":"10.3390\/ijms241411546","type":"journal-article","created":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T01:31:32Z","timestamp":1689643892000},"page":"11546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Suppression of NASH-Related HCC by Farnesyltransferase Inhibitor through Inhibition of Inflammation and Hypoxia-Inducible Factor-1\u03b1 Expression"],"prefix":"10.3390","volume":"24","author":[{"given":"Kohei","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomokazu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1553-2598","authenticated-orcid":false,"given":"Keita","family":"Kai","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohei","family":"Matsufuji","sequence":"additional","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kotaro","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Kitajima","sequence":"additional","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"},{"name":"Department of Surgery, National Hospital Organization Higashisaga Hospital, Saga 849-0101, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Manabe","sequence":"additional","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Noshiro","sequence":"additional","affiliation":[{"name":"Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Singh, G.M., Danaei, G., Farzadfar, F., Stevens, G.A., Woodward, M., Wormser, D., Kaptoge, S., Whitlock, G., Qiao, Q., and Lewington, S. 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