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利拉鲁肽,一种胰高血糖素样肽-1类似物,可诱导肝癌细胞系(HepG2)发生自噬和衰老。

Liraglutide, a glucagon-like peptide-1 analog, induce autophagy and senescence in HepG2 cells.

作者信息

Krause Gabriele Catyana, Lima Kelly Goulart, Dias Henrique Bregolin, da Silva Elisa Feller Gonçalves, Haute Gabriela Viegas, Basso Bruno Souza, Gassen Rodrigo Benedetti, Marczak Elisa Simon, Nunes Rafaela Sole Bach, de Oliveira Jarbas Rodrigues

机构信息

Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil.

Laboratório de Pesquisa em Biofísica Celular e Inflamação, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil.

出版信息

Eur J Pharmacol. 2017 Aug 15;809:32-41. doi: 10.1016/j.ejphar.2017.05.015. Epub 2017 May 10.

Abstract

It has been reported that glucagon-like peptide-1 (GLP-1) agents have been associated with both the increased risk of cancer and inhibition of tumor growth and metastases. The aim of this study is to evaluate the effect of liraglutide on hepatocellular carcinoma cells - HepG2. Cytometry was used to evaluate mechanism related to decreased cell proliferation. Nuclear staining and morphometric analysis were also used to verify the process that was taking place after treatment with liraglutide, and in order to better understand the mechanism, TGF-β1 was performed. HepG2 cells decreased proliferation after liraglutide treatment without altering oxidative stress levels. Liraglutide was able to induce autophagy and senescence through the increase of TGF-β1 which possibly explains the growth decrease. We have demonstrated that liraglutide has an antiproliferative effect in HepG2 cells inducing autophagy and senescence by the increase of TGF-β1.

摘要

据报道,胰高血糖素样肽-1(GLP-1)药物与癌症风险增加以及肿瘤生长和转移的抑制均有关联。本研究的目的是评估利拉鲁肽对肝癌细胞——HepG2的影响。采用细胞计数法评估与细胞增殖减少相关的机制。还使用细胞核染色和形态计量分析来验证利拉鲁肽处理后发生的过程,并且为了更好地理解该机制,进行了转化生长因子-β1(TGF-β1)相关研究。利拉鲁肽处理后HepG2细胞增殖减少,且氧化应激水平未改变。利拉鲁肽能够通过增加TGF-β1诱导自噬和衰老,这可能解释了其生长抑制作用。我们已经证明,利拉鲁肽在HepG2细胞中具有抗增殖作用,通过增加TGF-β1诱导自噬和衰老。

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