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  

作　　者：Yuanyuan Wang Bin Wei Danping Wang Jingjing Wu Jianhua Gao Haiqing Zhong Yang Sun Qiang Xu Wen Liu Yanhong Gu Wenjie Guo 

机构地区：[1]Department of Oncology,the First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China [2]Cancer Rehabilitation Center,Jiangsu Province Hospital,Nanjing 210029,China [3]Department of Oncology,the Affiliated Huai’an No.1 People’s Hospital of Nanjing Medical University,Huai'an 223300,China [4]State Key Laboratory of Pharmaceutical Biotechnology,School of Life Sciences,Nanjing University,Nanjing 210023,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第1期262-273,共12页药学学报（英文版）

基　　金：supported by National Natural Science Foundation of China(81871944,81572389,81922067);Jiangsu 333 project(BRA2016517,China);Natural Science Foundation of Jiangsu Province(BK20190306,China);Jiangsu Province Key Medical Talents(ZDRCA2016026,China);Priority Academic Program Development of Jiangsu Higher Education Institutions and Fundamental Research Funds for the Central Universities(14380114,China)。

摘　　要：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(ds DNA) from the intestine, leading to cyclic-GMP-AMP synthase(c GAS)-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 ds DNA-c GAS-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.

关 键 词：CPT-11 Gastrointestinal mucositis ANDROGRAPHOLIDE Homologous recombination cGAS-STING 

分 类 号：R285[医药卫生—中药学]