Small molecule GL-V9 protects against colitis-associated colorectal cancer by limiting NLRP3 inflammasome through autophagy

小分子 GL-V9 通过自噬限制 NLRP3 炎症小体来预防结肠炎相关的结直肠癌

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作者:Yue Zhao, Qinglong Guo, Kai Zhao, Yuxin Zhou, Wenjun Li, Chuyue Pan, Lei Qiang, Zhiyu Li, Na Lu

Abstract

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.

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