High efficacy of intravesical treatment of metformin on bladder cancer in preclinical model

Oncotarget
Mei PengXiaoping Yang

Abstract

Anticancer potential of metformin has been extensively studied. However, its anticancer clinical use remains yet to be approved since sufficient concentration on target organs could not be achieved via conventional administration. To overcome this drawback, we aim to examine the efficiency of novel intravesical treatment of metformin on syngeneic orthotopic preclinical model. Three human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. AMPK pathway including AKT, Erk and S6K was examined by western blot and further explored by regulating activated levels using specific inhibitors. In vivo efficacy was determined by Kaplan-Meier survival curves and measurements of body and bladder weights plus tumor biomarkers. Lactic acid and metformin levels of plasma were measured by standard procedures. The results demonstrated that metformin activated AMPK and decreased phosphorylation of Akt and Erk. Furthermore, combinations of metformin with either Akt or Erk inhibitors synergistically diminished cancer proliferation, suggesting the involvement of Akt- and Erk- related pathways. Intravesical metformin 26 and 104 mg/kg, twice per week demonstrated a rapid elimination of ...Continue Reading

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Citations

Mar 8, 2018·Journal of Cellular and Molecular Medicine·Qiongli SuXiaoping Yang
Nov 3, 2016·Nature Reviews. Clinical Oncology·Adi J Klil-DroriMichael N Pollak
Jul 31, 2018·Expert Review of Endocrinology & Metabolism·Lev M Berstein
Dec 16, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Min XinYanhong Guo
May 7, 2021·ACS Biomaterials Science & Engineering·Ahmad KabhaEyal Zussman

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Methods Mentioned

BETA
xenograft

Software Mentioned

Image J
CompuSyn

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