Small molecule GL-V9 protects against colitis-associated colorectal cancer by limiting NLRP3 inflammasome through autophagy
Small molecule GL-V9 protects against colitis-associated colorectal cancer by limiting NLRP3 inflammasome through autophagy
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DOI：
10.1080/2162402x.2017.1375640
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发表时间：
2018-01-01
期刊：
影响因子：
7.2
通讯作者：
Lu, Na
中科院分区：
文献类型：
--
作者：
Zhao, Yue;Guo, Qinglong;Lu, Na
新的证据表明，NLRP3 炎症小体提供了结肠炎相关结直肠癌和炎症性肠病之间的联系。 AMPK 激活可在巨噬细胞中诱导自噬，并调节 NLRP3 炎症小体以维持细胞内稳态。在这里，我们报道了一种小分子 AMPK 激活剂 (GL-V9) 在体外和体内对巨噬细胞发挥有效的抗炎作用，从而引发对降解的 NLRP3 炎性体的自噬。 GL-V9 治疗可预防结肠炎和结肠炎相关结直肠癌的肿瘤发生。这表明 GL-V9 可能是治疗结肠炎相关结直肠癌临床评估的一个有趣的候选者。
Emerging evidence suggests that NLRP3 inflammasome provides a link between colitis-associated colorectal cancer and inflammatory bowel diseases. Autophagy is induced in macrophages by AMPK activation and regulates NLRP3 inflammasome to maintain intracellular homeostasis. Here we report that a small-molecule AMPK activator (GL-V9) exerts potent anti-inflammatory effects on macrophages invitro and in vivo, which trigger autophagy to degraded NLRP3 inflammasome. Treatment with GL-V9 protected against colitis and tumorigenesis in colitis-associated colorectal cancer. This suggests that GL-V9 may be an interesting candidate for clinical evaluation in the treatment of colitis-associated colorectal cancer.