Early treatment with metformin induces resistance against tumor growth in adult rats

Cancer Biol Ther. 2015;16(6):958-64. doi: 10.4161/15384047.2014.962968. Epub 2015 May 29.

Abstract

It is known that antidiabetic drug metformin, which is used worldwide, has anti-cancer effects and can be used to prevent cancer growth. We tested the hypothesis that tumor cell growth can be inhibited by early treatment with metformin. For this purpose, adult rats chronically treated with metformin in adolescence or in adulthood were inoculated with Walker 256 carcinoma cells. Adult rats that were treated with metformin during adolescence presented inhibition of tumor growth, and animals that were treated during adult life did not demonstrate any changes in tumor growth. Although we do not have data to disclose a molecular mechanism to the preventive metformin effect, we present, for the first time, results showing that cancer growth in adult life is dependent on early life intervention, thus supporting a new therapeutic prevention for cancer.

Keywords: AUC, area under the curve; HOMA-IR, homeostasis model assessment of insulin resistance; HOMA-β, homeostasis model assessment of β-cell function; LBW, body weight loss; MHC-I, major histocompatibility complex class I; NAL, nasal anal length; VEGF, vascular endothelial growth factor.; Walker 256 tumor; adolescence; antidiabetic; early treatment; metformin; prevention; tumor growth inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Disease Models, Animal
  • Drug Resistance, Neoplasm*
  • Female
  • Heterografts
  • Male
  • Metformin / administration & dosage
  • Metformin / pharmacology*
  • Neoplasms / drug therapy
  • Neoplasms / pathology*
  • Rats

Substances

  • Antineoplastic Agents
  • Metformin

Grants and funding

This research was supported by grants from the Brazilian Research National Foundation: The Conselho National de Desenvolvimento Científico e Tecnológico (CNPq), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Paraná State Research Foundation (Fundação Araucária).