{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:27:40Z","timestamp":1787761660319,"version":"build-2784847793"},"reference-count":47,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"John Hunter Hospital Charitable Trust"},{"DOI":"10.13039\/501100001081","name":"Hunter Medical Research Institute","doi-asserted-by":"crossref","award":["G2200126"],"award-info":[{"award-number":["G2200126"]}],"id":[{"id":"10.13039\/501100001081","id-type":"DOI","asserted-by":"crossref"}]},{"name":"ARC Future Fellowships","award":["FT1500100179"],"award-info":[{"award-number":["FT1500100179"]}]},{"name":"ARC Future Fellowships","award":["G1601252"],"award-info":[{"award-number":["G1601252"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Endometrial cancers increase expression of the renin\u2013angiotensin system (RAS). This study aimed to determine if inhibiting the RAS would reduce the viability and proliferation of endometrial cancer cells. The expression of RAS genes was measured in three endometrial epithelial adenocarcinoma cell lines (Ishikawa, HEC-1-A, AN3CA). Ishikawa cells had the highest expression of REN, ACE, and AGTR1 mRNA. AGT mRNA and protein levels were most abundant in HEC-1-A cells. We then determined the effects of drugs that inhibit the action of renin (VTP-27999 and aliskiren) or angiotensin-converting enzyme (perindoprilat) or block the angiotensin II type 1 receptor (losartan and telmisartan). Overall, VTP-27999, aliskiren, perindoprilat, and losartan had minimal effects on cell viability in all three cell lines, and combinations of these drugs did not have any effect. Telmisartan (a dual angiotensin receptor blocker and PPAR-\u03b3 agonist) significantly reduced the viability of all three cell lines and reduced the proliferation of both Ishikawa and AN3CA cells. Telmisartan was more effective than troglitazone (PPAR-\u03b3 agonist) in Ishikawa and HEC-1-A cells. RAS inhibitors were most effective in Ishikawa cells, which had the highest levels of RAS expression. Therefore, levels of RAS expression in endometrial cancers might indicate the potential efficacy of RAS drugs.<\/jats:p>","DOI":"10.3390\/ijms262210968","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:10:45Z","timestamp":1763025045000},"page":"10968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Inhibitors of the Activity of the Circulating Renin\u2013Angiotensin System on the Growth and Proliferation of Endometrial Cancer Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Sarah J.","family":"Delforce","sequence":"first","affiliation":[{"name":"School of Medicine and Public Health, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW 2308, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riazuddin","family":"Mohammed","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Cancer Detection and Therapy Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0837-2793","authenticated-orcid":false,"given":"Tess L.","family":"Symington","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Women\u2019s Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"R&D, Beroni Group Ltd., Sydney, NSW 2000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole M.","family":"Verrills","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Cancer Detection and Therapy Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenie R.","family":"Lumbers","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Women\u2019s Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6770-0496","authenticated-orcid":false,"given":"Kirsty G.","family":"Pringle","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences and Pharmacy, College of Health, Medicine and Wellbeing, University of Newcastle, Newcastle, NSW 2308, Australia"},{"name":"Women\u2019s Health Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1530\/REP-09-0411","article-title":"A cancer stem cell origin for human endometrial carcinoma?","volume":"140","author":"Hubbard","year":"2010","journal-title":"Reproduction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1053\/j.sult.2019.04.001","article-title":"Imaging and Staging of Endometrial Cancer","volume":"40","author":"Faria","year":"2019","journal-title":"Semin. 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