DNA damage repair promotion in colonic epithelial cells by andrographolide downregulated cGAS‒STING pathway activation and contributed to the relief of CPT-11-induced intestinal mucositis

Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA (dsDNA) from the intestine, leading to cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination (HR) repair and downregulate dsDNA‒cGAS‒STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.

The role of Toll-like receptors in chemoradiotherapy-induced gastrointestinal mucositis / 口腔疾病防治

@#Mucositis is a common gastrointestinal complication in cancer patients undergoing chemoradiotherapy, including oral mucositis and gastrointestinal mucositis, with clinical manifestations of oral ulcers, vomiting, diarrhea and pain that seriously reduce the quality of life of patients and even affect anticancer therapy. Toll-like receptor (TLR) are important receptors involved in innate immunity and in the development of chemoradiation-induced mucositis by mediating the effect between microorganisms and the host. A comprehensive understanding of the role of TLR in mucositis is helpful to guide the prevention and treatment of mucositis. This paper reviews the available studies on TLR and mucositis. The results of the literature review indicate that different TLR have different roles in chemoradiation-induced mucositis: TLR2 is an important receptor in the inflammatory cascade of chemoradiation-induced mucositis; TLR4 activation can increase gastrointestinal mucosal inflammation and lead to oral epithelial ulceration; TLR5 agonists can reduce the degree of radiation-induced mucositis damage; and antagonizing or knocking out TLR9 can reduce chemoradiation-induced gastrointestinal mucositis. However, no TLR agonists or inhibitors have yet been applied in clinical practice, and additional studies are needed to explore the role of different TLR in mucositis in the future to provide a reference for the precise prevention and treatment of chemoradiation-induced mucositis.

Research progress on probiotics for the prevention and treatment of oral and gastrointestinal chemoradiotherapy mucositis / 口腔疾病防治

@#http://www.kqjbfz.com/article/2021/2096-1456/2096-1456-29-8-567.shtml