{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T17:27:30Z","timestamp":1784654850632,"version":"3.55.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2018R1D1A1B07051225"],"award-info":[{"award-number":["2018R1D1A1B07051225"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2021R1F1A1064309"],"award-info":[{"award-number":["2021R1F1A1064309"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2019M3E5D1A01069349"],"award-info":[{"award-number":["2019M3E5D1A01069349"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Science and ICT","award":["2018R1D1A1B07051225"],"award-info":[{"award-number":["2018R1D1A1B07051225"]}]},{"name":"Ministry of Science and ICT","award":["2021R1F1A1064309"],"award-info":[{"award-number":["2021R1F1A1064309"]}]},{"name":"Ministry of Science and ICT","award":["2019M3E5D1A01069349"],"award-info":[{"award-number":["2019M3E5D1A01069349"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Renal cell carcinoma (RCC) frequently recurs or metastasizes after surgical resection. Everolimus, an mTOR inhibitor, is used as a second-line treatment, but the response of RCC to everolimus is insufficient. Metformin is an antidiabetic drug; recent reports have indicated its anti-cancer effects in various cancers, and it is known to have synergistic effects with other drugs. We investigated the possibility of coadministering everolimus and metformin as an effective treatment for RCC. RCC cells treated with a combination of the two drugs showed significantly inhibited cell viability, cell migration, and invasion, and increased apoptosis compared to those treated with each drug alone. An anti-cancer synergistic effect was also confirmed in the xenograft model. Transcriptome analysis for identifying the underlying mechanism of the combined treatment showed the downregulation of mitochondrial fusion genes and upregulation of mitochondrial fission genes by the combination treatment. Changes in mitochondrial dynamics following the combination treatment were observed using LysoTracker, LysoSensor, and JC-1 staining. In conclusion, the combination of everolimus and metformin inhibited RCC growth by disrupting mitochondrial dynamics. Therefore, we suggest that a treatment combining metformin and everolimus disrupts mitochondrial dynamics in RCC, and may be a novel strategy for RCC treatment.<\/jats:p>","DOI":"10.3390\/genes13071211","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T21:15:52Z","timestamp":1657142152000},"page":"1211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synergic Effect of Metformin and Everolimus on Mitochondrial Dynamics of Renal Cell Carcinoma"],"prefix":"10.3390","volume":"13","author":[{"given":"Seong-Hwi","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Urology, Hanyang University College of Medicine, Seoul 04763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7961-8393","authenticated-orcid":false,"given":"Kwang-Suk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Urology, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Ji","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Urology, Hanyang University College of Medicine, Seoul 04763, Korea"},{"name":"Department of Translational Medicine, Hanyang University Graduate School, Seoul 04763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Yul","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Urology, Hanyang University College of Medicine, Seoul 04763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woong-Kyu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Urology, Yonsei University College of Medicine, Seoul 03722, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8059-6649","authenticated-orcid":false,"given":"Young-Eun","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Urology, Hanyang University College of Medicine, Seoul 04763, Korea"},{"name":"Department of Medical and Digital Engineering, Hanyang University Graduate School, Seoul 04763, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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