PDF(Pubmed)
Abstract：
Glucagon-like peptide-1 (GLP-1) regulates glycemic excursions by augmenting insulin production and inhibiting glucagon secretion. Liraglutide, a long-acting GLP-1 analog, can improve glycemic control for treating type 2 diabetes and prevent neutrophil extravasation in inflammation. Here, we explored the role of liraglutide in the development and therapy of murine lung and liver cancers. In this study, liraglutide substantially decreased circulating neutrophil extracellular trap (NET) markers myeloperoxidase, elastase, and dsDNA in Lewis lung cancer (LLC) and Hepa1-6 tumor-bearing mice. Furthermore, liraglutide downregulated NETs and reactive oxygen species (ROS) of neutrophils in the tumor microenvironment. Functionally, in vitro experiments showed that liraglutide reduced NET formation by inhibiting ROS. In addition, we showed that liraglutide enhanced the anti-tumoral efficiency of programmed cell death-1 (PD-1) inhibition in LLC and Hepa1-6 tumor-bearing C57BL/6 mice. However, the removal of NETs significantly weakened the antitumor efficiency of liraglutide. We further demonstrated that the long-term antitumor CD8+ T cell responses induced by the combination therapy rejected rechallenges by respective tumor cell lines. Taken together, our findings suggest that liraglutide may promote the anti-tumoral efficiency of PD-1 inhibition by reducing NETs in lung and liver cancers.
摘要：
胰高血糖素样肽-1(GLP-1)通过增加胰岛素产生和抑制胰高血糖素分泌来调节血糖漂移。利拉鲁肽,长效GLP-1类似物,可以改善2型糖尿病患者的血糖控制，防止炎症中的中性粒细胞外渗。这里,我们探讨了利拉鲁肽在小鼠肺癌和肝癌的发展和治疗中的作用。在这项研究中,利拉鲁肽显著降低循环中性粒细胞胞外捕获（NET）标志物髓过氧化物酶，弹性蛋白酶,和dsDNA在LLC和Hepa1-6荷瘤小鼠中。此外，利拉鲁肽下调肿瘤微环境中中性粒细胞的NETs和活性氧（ROS）。功能上,体外实验表明，利拉鲁肽通过抑制ROS减少NET的形成。此外,我们发现利拉鲁肽在LLC和Hepa1-6荷瘤C57BL/6小鼠中增强了PD-1抑制的抗肿瘤效率。然而,NETs的去除显著削弱了利拉鲁肽的抗肿瘤功效。我们进一步证明，联合疗法诱导的长期抗肿瘤CD8T细胞应答拒绝了各自肿瘤细胞系的再攻击。一起来看,我们的研究结果表明,利拉鲁肽可能通过减少肺癌和肝癌中的NETs来促进PD-1抑制的抗肿瘤功效.
