1. Academic Validation
  2. 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.
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.

Figures
Products