Cellular Physiology and Biochemistry (May 2017)

Chronic Glibenclamide Treatment Attenuates Walker-256 Tumour Growth in Prediabetic Obese Rats

  • Claudinéia Conationi da Silva Franco,
  • Carina Previate,
  • Kátia Gama de Barros Machado,
  • Silvano Piovan,
  • Rosiane Aparecida Miranda,
  • Kelly Valério Prates,
  • Veridiana Mota Moreira,
  • Júlio Cezar de Oliveira,
  • Luiz Felipe Barella,
  • Rodrigo Mello Gomes,
  • Flávio Andrade Francisco,
  • Isabela Peixoto Martins,
  • Audrei Pavanello,
  • Tatiane Aparecida Ribeiro,
  • Laize Peron Tófolo,
  • Ananda Malta,
  • Aline Amenencia de Souza,
  • Vander Silva Alves,
  • Sandra da Silva Silveira,
  • Maria Raquel Marçal Natali,
  • Jean Carlos Fernando Besson,
  • Hely de Morais,
  • Helenir Medri de Souza,
  • Juliane Rocha de Sant Anna,
  • Marialba Avezum Alves de Castro Prado,
  • Paulo Cezar de Freitas Mathias

DOI
https://doi.org/10.1159/000477117
Journal volume & issue
Vol. 42, no. 1
pp. 81 – 90

Abstract

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Background/Aims: The sulphonylurea glibenclamide (Gli) is widely used in the treatment of type 2 diabetes. In addition to its antidiabetic effects, low incidences of certain types of cancer have been observed in Gli-treated diabetic patients. However, the mechanisms underlying this observation remain unclear. The aim of the present work was to evaluate whether obese adult rats that were chronically treated with an antidiabetic drug, glibenclamide, exhibit resistance to rodent breast carcinoma growth. Methods: Neonatal rats were treated with monosodium L-glutamate (MSG) to induce prediabetes. Control and MSG groups were treated with Gli (2 mg/kg body weight/day) from weaning to 100 days old. After Gli treatment, the control and MSG rats were grafted with Walker-256 tumour cells. After 14 days, grafted rats were euthanized, and tumour weight as well as glucose homeostasis were evaluated. Results: Treatment with Gli normalized tissue insulin sensitivity and glucose tolerance, suppressed fasting hyperinsulinaemia, reduced fat tissue accretion in MSG rats, and attenuated tumour growth by 27% in control and MSG rats. Conclusions: Gli treatment also resulted in a large reduction in the number of PCNA-positive tumour cells. Although treatment did improve the metabolism of pre-diabetic MSG-rats, tumour growth inhibition may be a more direct effect of glibenclamide.

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