Metformin Amplifies Chemotherapy-induced Ampk Activation And Antitumoral Growth

dc.creatorRocha G.Z.
dc.creatorDias M.M.
dc.creatorRopelle E.R.
dc.creatorOsorio-Costa F.
dc.creatorRossato F.A.
dc.creatorVercesi A.E.
dc.creatorSaad M.J.A.
dc.creatorCarvalheira J.B.C.
dc.date2011
dc.date2015-06-30T20:43:08Z
dc.date2015-11-26T14:54:11Z
dc.date2015-06-30T20:43:08Z
dc.date2015-11-26T14:54:11Z
dc.date.accessioned2018-03-28T22:06:02Z
dc.date.available2018-03-28T22:06:02Z
dc.identifier
dc.identifierClinical Cancer Research. , v. 17, n. 12, p. 3993 - 4005, 2011.
dc.identifier10780432
dc.identifier10.1158/1078-0432.CCR-10-2243
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-79959207505&partnerID=40&md5=4ca8405435ef4947287ba0b22e62f809
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/108971
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/108971
dc.identifier2-s2.0-79959207505
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1255085
dc.descriptionPurpose: Metformin is a widely used antidiabetic drug whose anticancer effects, mediated by the activation of AMP-activated protein kinase (AMPK) and reduction of mTOR signaling, have become noteworthy. Chemotherapy produces genotoxic stress and induces p53 activity, which can cross-talk with AMPK/mTOR pathway. Herein, we investigate whether the combination of metformin and paclitaxel has an effect in cancer cell lines. Experimental Design: Human tumors were xenografted into severe combined immunodeficient (SCID) mice and the cancer cell lines were treated with only paclitaxel or only metformin, or a combination of both drugs. Western blotting, flow cytometry, and immunohistochemistry were then used to characterize the effects of the different treatments. Results: The results presented herein show that the addition of metformin to paclitaxel leads to quantitative potentialization of molecular signaling through AMPK and a subsequent potent inhibition of the mTOR signaling pathway. Treatment with metformin and paclitaxel resulted in an increase in the number of cells arrested in the G2-M phase of the cell cycle, and decreased the tumor growth and increased apoptosis in tumor-bearing mice, when compared with individual drug treatments. Conclusion: We have provided evidence for a convergence of metformin and paclitaxel induced signaling at the level of AMPK. This mechanism shows how different drugs may cooperate to augment antigrowth signals, and suggests that target activation of AMPK by metformin may be a compelling ally in cancer treatment. ©2011 AACR.
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dc.languageen
dc.publisher
dc.relationClinical Cancer Research
dc.rightsfechado
dc.sourceScopus
dc.titleMetformin Amplifies Chemotherapy-induced Ampk Activation And Antitumoral Growth
dc.typeArtículos de revistas


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