Screening of and mechanism underlying the action of serum- and glucocorticoid-regulated kinase 3-targeted drugs against estrogen receptor-positive breast cancer

作者全名："Zhou, Duanfang; Yu, Xiaoping; Song, Yi; Zeng, Hongfang; Zhang, Huan; Chen, Bo; Wang, Yalan; Li, Hongyao; Liu, Xu; He, Qichen; Li, Xiaoli; Zhou, Weiying"

作者地址："[Zhou, Duanfang; Yu, Xiaoping; Song, Yi; Zeng, Hongfang; Zhang, Huan; Chen, Bo; Liu, Xu; He, Qichen; Li, Xiaoli; Zhou, Weiying] Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China; [Zhou, Duanfang; Yu, Xiaoping; Song, Yi; Zeng, Hongfang; Zhang, Huan; Chen, Bo; Liu, Xu; He, Qichen; Li, Xiaoli; Zhou, Weiying] Chongqing Key Lab Drug Metab, Chongqing 400016, Peoples R China; [Zhou, Duanfang; Yu, Xiaoping; Song, Yi; Zeng, Hongfang; Zhang, Huan; Chen, Bo; Liu, Xu; He, Qichen; Li, Xiaoli; Zhou, Weiying] Key Lab Biochem & Mol Pharmacol Chongqing, Chongqing 400016, Peoples R China; [Wang, Yalan; Li, Hongyao] Chongqing Med Univ, Sch Pharm, Chongqing 400016, Peoples R China"

通信作者："Li, XL; Zhou, WY (通讯作者)，Chongqing Med Univ, Coll Pharm, Dept Pharmacol, Chongqing 400016, Peoples R China."

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000833536500001

JCR分区：Q1

影响因子：5

年份：2022

卷号：927

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文献类型：Article

关键词：Breast cancer; Computer-aided drug discovery/design; SGK3; Estrogen receptor; Autophagy

摘要："Breast cancer is the most common cancer in women. Serum and glucocorticoid-regulated kinase 3 (SGK3) promotes the progression and drug resistance of estrogen receptor-positive (ER+) breast cancer. Therefore, SGK3 is a promising therapeutic target for the treatment of ER + breast cancer. In this study, we used computer-aided drug discovery/design to perform a virtual screening of SGK3 inhibitors from the ZINC database. The results of MTT assay, real-time cell proliferation analysis, colony formation assay, transwell migration assay, and orthotopic implantation model show that Zinc-09 inhibited the proliferation and migration of ER + breast cancer cells in vivo and in vitro. Furthermore, Zinc-09 decreased SGK3 expression, and knockdown of SGK3 by siRNA reversed the inhibitory effect of Zinc-09 in MCF-7 cells. Moreover, Zinc-09 treatment induced G1 phase arrest and autophagic cell death. Taken together, Zinc-09 can suppress ER + breast cancer. This study provides an experimental and theoretical basis for the research and development of new anti-ER + breast cancer drugs."

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