期刊
ACTA PHARMACEUTICA SINICA B
卷 12, 期 1, 页码 262-273出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2021.03.043
关键词
CPT-11; Gastrointestinal mucositis; Andrographolide; Homologous recombination; cGAS-STING
资金
- National Natural Science Foundation of China [81871944, 81572389, 81922067]
- Jiangsu 333 project, China [BRA2016517]
- Natural Science Foundation of Jiangsu Province, China [BK20190306]
- Jiangsu Province Key Medical Talents, China [ZDRCA2016026]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Fundamental Research Funds for the Central Universitie, China [14380114]
Andrographolide can alleviate CPT-11-induced colitis in tumor-bearing mice without affecting the tumor suppression effect of CPT-11. This may be achieved by promoting homologous recombination repair and downregulating dsDNA-cGAS-STING signaling.
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. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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