{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:21:51Z","timestamp":1777454511834,"version":"3.51.4"},"reference-count":76,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"PDUPT Research Grant","award":["NKB-787\/UN2.RST \/HKP.05.00\/2022"],"award-info":[{"award-number":["NKB-787\/UN2.RST \/HKP.05.00\/2022"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Breast Cancer\ufffd(Auckl)"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>Backgrounds:<\/jats:title>\n                    <jats:p>About 25% to 30% of estrogen receptor (ER)-positive breast cancer patients develop resistance to endocrine therapy. Human epidermal growth factor receptor 2 (HER2) has been shown to cooperate with several growth factors that regulate cellular energy metabolism, including the insulin-like growth factor 1 receptor (IGF-1R).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>As the first-line therapy for type 2 diabetes mellitus (T2DM) patients, metformin is widely known to inhibit the metabolic reprogramming of cancer cells. This study aims to investigate metformin\u2019s efficacy in inhibiting endocrine resistance related to genes regulating energy metabolism in both ER-positive and ER-negative breast cancer cell lines under hyperglycemic conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and methods:<\/jats:title>\n                    <jats:p>MDA-MB-361 (ER-positive, HER2-positive) and SKBR3 (ER-negative, HER2-positive) cancer cell lines were used to represent ER status. Cell viability and cell survival rate were measured using the colorimetric assay of Cell Counting Kit-8. All mRNA levels were quantified using real-time quantitative polymerase chain reaction preceded by reverse transcription. A P value of &lt;.05 was considered statistically significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Unlike MDA-MB-361, SKBR3 were found to acquire resistance upon metformin treatment in hyperglycemic conditions. Moreover, the mRNA expression of IGF-1R and its downstream signaling, such as the mammalian target of rapamycin (mTOR), was not affected by metformin. Meanwhile, the mRNA expression level of ribosomal S6 kinase 1 (S6K1) was upregulated, whereas forkhead box O1 (FOXO1) was downregulated after metformin treatment in hyperglycemic conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>This preliminary study suggests that an alternative pathway of metformin resistance may exist in the absence of ER\u03b1. Therefore, relying solely on metformin may be inadequate to inhibit the aggressiveness of breast cancer cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/11782234241240173","type":"journal-article","created":{"date-parts":[[2024,4,9]],"date-time":"2024-04-09T00:46:18Z","timestamp":1712623578000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Estrogen Receptor Is Required for Metformin-Induced Apoptosis in Breast Cancer Cells Under Hyperglycemic Conditions"],"prefix":"10.1177","volume":"18","author":[{"given":"Andisyah Putri","family":"Sekar","sequence":"first","affiliation":[{"name":"Pharmacology and Clinical Pharmacy Laboratory, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Septia","family":"Nurmala","sequence":"additional","affiliation":[{"name":"Pharmacology and Clinical Pharmacy Laboratory, Faculty of 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