慢性格列本脲治疗可减轻糖尿病前期肥胖大鼠Walker-256肿瘤的生长。
Chronic Glibenclamide Treatment Attenuates Walker-256 Tumour Growth in Prediabetic Obese Rats.
作者信息
da Silva Franco Claudinéia Conationi, Previate Carina, de Barros Machado Kátia Gama, Piovan Silvano, Miranda Rosiane Aparecida, Prates Kelly Valério, Moreira Veridiana Mota, de Oliveira Júlio Cezar, Barella Luiz Felipe, Gomes Rodrigo Mello, Francisco Flávio Andrade, Martins Isabela Peixoto, Pavanello Audrei, Ribeiro Tatiane Aparecida, Tófolo Laize Peron, Malta Ananda, de Souza Aline Amenencia, Alves Vander Silva, da Silva Silveira Sandra, Marçal Natali Maria Raquel, Fernando Besson Jean Carlos, de Morais Hely, de Souza Helenir Medri, de Sant Anna Juliane Rocha, Alves de Castro Prado Marialba Avezum, de Freitas Mathias Paulo Cezar
机构信息
Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, Brazil.
Laboratory of Physiology, Department of Physiological Sciences, State University of Maringá, Maringá, Brazil.
出版信息
Cell Physiol Biochem. 2017;42(1):81-90. doi: 10.1159/000477117. Epub 2017 May 11.
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.
背景/目的：磺脲类药物格列本脲（Gli）广泛用于2型糖尿病的治疗。除了其抗糖尿病作用外，在接受Gli治疗的糖尿病患者中还观察到某些类型癌症的发病率较低。然而，这一观察结果背后的机制仍不清楚。本研究的目的是评估长期接受抗糖尿病药物格列本脲治疗的肥胖成年大鼠是否对啮齿动物乳腺癌生长具有抗性。
方法
用L-谷氨酸单钠（MSG）处理新生大鼠以诱导糖尿病前期。对照组和MSG组从断奶至100日龄用Gli（2mg/kg体重/天）治疗。Gli治疗后，将对照组和MSG大鼠接种Walker-256肿瘤细胞。14天后，对移植大鼠实施安乐死，并评估肿瘤重量以及葡萄糖稳态。
结果
Gli治疗使组织胰岛素敏感性和葡萄糖耐量正常化，抑制空腹高胰岛素血症，减少MSG大鼠的脂肪组织积聚，并使对照组和MSG大鼠的肿瘤生长减少27%。
结论
Gli治疗还导致PCNA阳性肿瘤细胞数量大幅减少。虽然治疗确实改善了糖尿病前期MSG大鼠的代谢，但肿瘤生长抑制可能是格列本脲更直接的作用。
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