{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:27:53Z","timestamp":1787167673392,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,11,5]],"date-time":"2023-11-05T00:00:00Z","timestamp":1699142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP15K10915"],"award-info":[{"award-number":["JP15K10915"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16K15740"],"award-info":[{"award-number":["JP16K15740"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Hepato Biliary Pancreat"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer cells can alter glucose metabolism and regulate the expression of glucose transporters. Hepatoblastoma patients undergo cisplatin\u2010based chemotherapy; however, 22.3% of patients develop cisplatin resistance and thus face a poor prognosis. We hypothesized that glucose transporters are associated with acquiring cisplatin resistance with increasing sugar intake inhibiting glucose transporters could reduce cisplatin resistance in hepatoblastoma patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established cisplatin\u2010resistant HepG2 and HuH6 cells by continuous treatment with cisplatin. We evaluated the relationship between cisplatin resistance and glucose uptake. We used an expression array to select cisplatin\u2010resistant associated glucose transporters and selected sodium\u2010glucose cotransporter 2 (SGLT2). We used dapagliflozin as an SGLT2 inhibitor and evaluated glucose uptake and IC50 after dapagliflozin treatment in wild\u2010type and resistant hepatoblastoma cells in\u00a0vitro and in\u00a0vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found a strong relationship between cisplatin resistance and glucose uptake. Additionally, SGLT2 was upregulated in resistant cells after cisplatin treatment. After dapagliflozin treatment, glucose uptake and cisplatin resistance decreased in resistant cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cisplatin\u2010resistant hepatoblastoma cells exhibited upregulated SGLT2 expression and activated glucose uptake to survive under cisplatin stress. SGLT2 inhibition decreased cellular resistance to cisplatin. SGLT2 inhibition with cisplatin therapy could be a novel therapeutic strategy for cisplatin\u2010resistant hepatoblastoma patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jhbp.1391","type":"journal-article","created":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T02:16:32Z","timestamp":1699236992000},"page":"223-233","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["<scp>SGLT2<\/scp>\n                    is upregulated to acquire cisplatin resistance and\n                    <scp>SGLT2<\/scp>\n                    inhibition reduces cisplatin resistance in hepatoblastoma"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4549-2059","authenticated-orcid":false,"given":"Sunao","family":"Fujiyoshi","sequence":"first","affiliation":[{"name":"Department of Gastroenterological Surgery 1 Hokkaido University Graduate School of Medicine  Sapporo Hokkaido 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Medicine  Sapporo Hokkaido Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akinobu","family":"Taketomi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterological Surgery 1 Hokkaido University Graduate School of Medicine  Sapporo Hokkaido 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