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甘草次酸二钠通过靶向组蛋白去乙酰化酶6抑制胃癌细胞迁移。

Carbenoxolone disodium suppresses the migration of gastric cancer by targeting HDAC6.

作者信息

Song Zhiyu, Zhao Chenglong, Yan Jingjing, Jiang Dandan, Jia Gang

机构信息

Department of Pharmacy, Henan Provincial People's Hospital; People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China.

Department of Oncology, Henan Provincial People's Hospital; People's Hospital of Zhengzhou University, Zhengzhou, Henan, 450003, China.

出版信息

Future Med Chem. 2023 Feb;15(4):333-344. doi: 10.4155/fmc-2022-0246. Epub 2023 Mar 22.

Abstract

Because of the severe morbidity and mortality of gastric cancer, discovering new candidate drugs has been an urgent issue. The close association between histone deacetylase 6 (HDAC6) and gastric cancer makes the development of HDAC6-targeted anti-gastric cancer drugs a viable idea. Carbenoxolone disodium was identified as a novel HDAC6 inhibitor. Cellular thermal shift assay, surface plasmon resonance assay and molecular docking confirmed its binding ability to HDAC6. Cell viability, wound healing and transwell assays as well as animal studies have demonstrated that carbenoxolone disodium could block the proliferation and migration of gastric cancer cells MGC-803 and . This is the first report to indicate that carbenoxolone disodium could be an HDAC6 inhibitor with potential for treatment of gastric cancer.

摘要

由于胃癌具有严重的发病率和死亡率,发现新的候选药物一直是一个紧迫的问题。组蛋白去乙酰化酶6(HDAC6)与胃癌之间的密切关联使得开发针对HDAC6的抗胃癌药物成为一个可行的想法。甘草次酸钠被鉴定为一种新型的HDAC6抑制剂。细胞热迁移分析、表面等离子体共振分析和分子对接证实了其与HDAC6的结合能力。细胞活力、伤口愈合和Transwell分析以及动物研究表明,甘草次酸钠可以阻断胃癌细胞MGC-803的增殖和迁移。这是第一份表明甘草次酸钠可能是一种具有治疗胃癌潜力的HDAC6抑制剂的报告。

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