王明晋, 伏蓉, 姜慧敏, 金晶, 陈晓光. STING激动剂细胞筛选模型的建立和应用J. 药学学报, 2019,54(10): 1875-1880. doi: 10.16438/j.0513-4870.2019-0735
引用本文: 王明晋, 伏蓉, 姜慧敏, 金晶, 陈晓光. STING激动剂细胞筛选模型的建立和应用J. 药学学报, 2019,54(10): 1875-1880. doi: 10.16438/j.0513-4870.2019-0735
WANG Ming-jin, FU Rong, JIANG Hui-min, JIN Jing, CHEN Xiao-guang. Establishment and application of STING agonist in-vitro screening modelJ. Acta Pharmaceutica Sinica, 2019,54(10): 1875-1880. doi: 10.16438/j.0513-4870.2019-0735
Citation: WANG Ming-jin, FU Rong, JIANG Hui-min, JIN Jing, CHEN Xiao-guang. Establishment and application of STING agonist in-vitro screening modelJ. Acta Pharmaceutica Sinica, 2019,54(10): 1875-1880. doi: 10.16438/j.0513-4870.2019-0735

STING激动剂细胞筛选模型的建立和应用

Establishment and application of STING agonist in-vitro screening model

  • 摘要: 肿瘤免疫疗法已成为当今抗癌药物研发的重要领域,STING激动剂的研究为肿瘤免疫治疗提供了新思路。哺乳动物胞质中的核酸可有效引起固有免疫反应,近年大量研究证实cGAS-cGAMP-STING信号通路在胞浆DNA识别和免疫防御激活过程中发挥关键作用。cGAS-cGAMP-STING信号通路的异常与肿瘤的发生发展密切相关,是药物研发的热门靶点。本研究利用稳定表达cGAS-STING通路的THP-1-Dual细胞和稳定敲除STING的THP-1 KO-STING细胞,建立了荧光素酶检测的STING激动剂筛选模型。进一步应用阳性药物验证了本模型的准确性和灵敏度,为高通量筛选STING激动剂提供了简便、高效、准确的筛选平台。

     

    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.

     

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