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

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

  • Eur J Pharmacol. 2022 Jul 15;927:174982. doi: 10.1016/j.ejphar.2022.174982.
Duanfang Zhou 1,  Xiaoping Yu 1,  Yi Song 1,  Hongfang Zeng 1,  Huan Zhang 1,  Bo Chen 1,  Yalan Wang 2,  Hongyao Li 2,  Xu Liu 1,  Qichen He 1,  Xiaoli Li 3,  Weiying Zhou 4
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Drug Metabolism, Chongqing, 400016, China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, 400016, China.
  • 2 School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
  • 3 Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Drug Metabolism, Chongqing, 400016, China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, 400016, China. Electronic address: plum181181@126.com.
  • 4 Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, China; Chongqing Key Laboratory of Drug Metabolism, Chongqing, 400016, China; Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, 400016, China. Electronic address: wyzhou0118@163.com.
PMID: 35569550 DOI: 10.1016/j.ejphar.2022.174982
Abstract

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.

Keywords

Autophagy; Breast cancer; Computer-aided drug discovery/design; Estrogen receptor; SGK3.

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