Establishment and application of STING agonist in-vitro screening model
10.16438/j.0513-4870.2019-0735
- VernacularTitle:STING激动剂细胞筛选模型的建立和应用
- Author:
Ming-jin WANG
1
;
Rong FU
1
;
Hui-min JIANG
1
;
Jing JIN
1
;
Xiao-guang CHEN
1
Author Information
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines/Beijing Key Laboratory of Non-clinical Drug Metabolism and PK/PD Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
STING agonist;
THP-1 Dual cell;
screening model;
cancer;
immunotherapy
- From:
Acta Pharmaceutica Sinica
2019;54(10):1875-1880
- CountryChina
- Language:Chinese
-
Abstract:
Tumor immunotherapy is a critical field in the development of anticancer drugs. The research of stimulator of interferon genes (STING) agonist provides a new idea for immunotherapy. Innate immune response can effectively be induced by nucleic acids in mammalian cytoplasm. In recent years, a large number of studies have confirmed that the cGAS-cGAMP-STING signaling pathway plays a key role in cytoplasmic DNA recognition and immune defense activation. The dysfunction of cGAS-cGAMP-STING is closely related to the tumorigenesis, and is a potent target for drug development. In this study, based on THP-1 dual cells which are stably expressing cGAS-STING pathway and THP-1 KO-STING cells which are stably depleted STING, a screening method for STING agonists was established by detection of luciferase. Furthermore, the accuracy and sensitivity of the model were verified using positive compound, providing a simple, efficient and accurate screening platform for high-throughput screening of STING agonists.