{"title":"SGLT2被上调以获得顺铂耐药性，并且SGLT2抑制降低肝母细胞瘤中的顺铂耐药性。","authors":"Sunao Fujiyoshi, Shohei Honda, Momoko Ara, Takafumi Kondo, Nozomi Kobayashi, Akinobu Taketomi","doi":"10.1002/jhbp.1391","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Cancer cells can alter glucose metabolism and regulate the expression of glucose transporters. Hepatoblastoma patients undergo cisplatin-based 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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We established cisplatin-resistant 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-resistant associated glucose transporters and selected sodium-glucose cotransporter 2 (SGLT2). We used dapagliflozin as an SGLT2 inhibitor and evaluated glucose uptake and IC50 after dapagliflozin treatment in wild-type and resistant hepatoblastoma cells in vitro and in vivo.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Cisplatin-resistant 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-resistant hepatoblastoma patients.</p>\n </section>\n </div>","PeriodicalId":16056,"journal":{"name":"Journal of Hepato‐Biliary‐Pancreatic Sciences","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2023-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SGLT2 is upregulated to acquire cisplatin resistance and SGLT2 inhibition reduces cisplatin resistance in hepatoblastoma\",\"authors\":\"Sunao Fujiyoshi, Shohei Honda, Momoko Ara, Takafumi Kondo, Nozomi Kobayashi, Akinobu Taketomi\",\"doi\":\"10.1002/jhbp.1391\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Cancer cells can alter glucose metabolism and regulate the expression of glucose transporters. Hepatoblastoma patients undergo cisplatin-based 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We established cisplatin-resistant 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-resistant associated glucose transporters and selected sodium-glucose cotransporter 2 (SGLT2). We used dapagliflozin as an SGLT2 inhibitor and evaluated glucose uptake and IC50 after dapagliflozin treatment in wild-type and resistant hepatoblastoma cells in vitro and in vivo.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Cisplatin-resistant 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-resistant hepatoblastoma patients.</p>\\n </section>\\n </div>\",\"PeriodicalId\":16056,\"journal\":{\"name\":\"Journal of Hepato‐Biliary‐Pancreatic Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2023-11-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Hepato‐Biliary‐Pancreatic Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jhbp.1391\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Hepato‐Biliary‐Pancreatic Sciences","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jhbp.1391","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
SGLT2 is upregulated to acquire cisplatin resistance and SGLT2 inhibition reduces cisplatin resistance in hepatoblastoma
Background
Cancer cells can alter glucose metabolism and regulate the expression of glucose transporters. Hepatoblastoma patients undergo cisplatin-based 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.
Methods
We established cisplatin-resistant 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-resistant associated glucose transporters and selected sodium-glucose cotransporter 2 (SGLT2). We used dapagliflozin as an SGLT2 inhibitor and evaluated glucose uptake and IC50 after dapagliflozin treatment in wild-type and resistant hepatoblastoma cells in vitro and in vivo.
Results
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.
Conclusions
Cisplatin-resistant 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-resistant hepatoblastoma patients.
期刊介绍：
The Journal of Hepato-Biliary-Pancreatic Sciences (JHBPS) is the leading peer-reviewed journal in the field of hepato-biliary-pancreatic sciences. JHBPS publishes articles dealing with clinical research as well as translational research on all aspects of this field. Coverage includes Original Article, Review Article, Images of Interest, Rapid Communication and an announcement section. Letters to the Editor and comments on the journal’s policies or content are also included. JHBPS welcomes submissions from surgeons, physicians, endoscopists, radiologists, oncologists, and pathologists.
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