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dc.contributor.authorBRODOWSKA, KATARZYNAen_US
dc.contributor.authorTHEODOROPOULOU, SOFIAen_US
dc.contributor.authorHÖRSTE, MELISSA MEYER ZUen_US
dc.contributor.authorPASCHALIS, ELEFTHERIOS I.en_US
dc.contributor.authorTAKEUCHI, KIMIOen_US
dc.contributor.authorSCOTT, GORDONen_US
dc.contributor.authorRAMSEY, DAVID J.en_US
dc.contributor.authorKIERNAN, ELIZABETHen_US
dc.contributor.authorHOANG, MIENen_US
dc.contributor.authorCICHY, JOANNAen_US
dc.contributor.authorMILLER, JOAN W.en_US
dc.contributor.authorGRAGOUDAS, EVANGELOS S.en_US
dc.contributor.authorVAVVAS, DEMETRIOS G.en_US
dc.date.accessioned2014-11-03T17:40:25Z
dc.date.issued2014en_US
dc.identifier.citationBRODOWSKA, K., S. THEODOROPOULOU, M. M. Z. HÖRSTE, E. I. PASCHALIS, K. TAKEUCHI, G. SCOTT, D. J. RAMSEY, et al. 2014. “Effects of metformin on retinoblastoma growth in vitro and in vivo.” International Journal of Oncology 45 (6): 2311-2324. doi:10.3892/ijo.2014.2650. http://dx.doi.org/10.3892/ijo.2014.2650.en
dc.identifier.issn1019-6439en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13347612
dc.description.abstractRecent studies suggest that the anti-diabetic drug metformin may reduce the risk of cancer and have anti-proliferative effects for some but not all cancers. In this study, we examined the effects of metformin on human retinoblastoma cell proliferation in vitro and in vivo. Two different human retinoblastoma cell lines (Y79, WERI) were treated with metformin in vitro and xenografts of Y79 cells were established in nu/nu immune-deficient mice and used to assess the effects of pharmacological levels of metformin in vivo. Metformin inhibited proliferation of the retinoblastoma cells in vitro. Similar to other studies, high concentrations of metformin (mM) blocked the cell cycle in G0–G1, indicated by a strong decrease of G1 cyclins, especially cyclin D, cyclin-dependent kinases (4 and 6), and flow cytometry assessment of the cell cycle. This was associated with activation of AMPK, inhibition of the mTOR pathways and autophagy marker LC3B. However, metformin failed to suppress growth of xenografted tumors of Y79 human retinoblastoma cells in nu/nu mice, even when treated with a maximally tolerated dose level achieved in human patients. In conclusion, suprapharmacological levels (mM) of metformin, well above those tolerated in vivo, inhibited the proliferation of retinoblastoma cells in vitro. However, physiological levels of metformin, such as seen in the clinical setting, did not affect the growth of retinoblastoma cells in vitro or in vivo. This suggests that the potential beneficial effects of metformin seen in epidemiological studies may be limited to specific tumor types or be related to indirect effects/mechanisms not observed under acute laboratory conditions.en
dc.language.isoen_USen
dc.publisherD.A. Spandidosen
dc.relation.isversionofdoi:10.3892/ijo.2014.2650en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4215581/pdf/en
dash.licenseLAAen_US
dc.subjecttoxicityen
dc.subjectautophagyen
dc.subjectproliferationen
dc.subjectapoptosisen
dc.subjectcyclinen
dc.titleEffects of metformin on retinoblastoma growth in vitro and in vivoen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalInternational Journal of Oncologyen
dash.depositing.authorBRODOWSKA, KATARZYNAen_US
dc.date.available2014-11-03T17:40:25Z
dc.identifier.doi10.3892/ijo.2014.2650*
dash.authorsorderedfalse
dash.contributor.affiliatedHoang, Mien
dash.contributor.affiliatedGragoudas, Evangelos
dash.contributor.affiliatedBrodowska, Katarzyna
dash.contributor.affiliatedMiller, Joan
dash.contributor.affiliatedVavvas, Demetrios


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