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
  • 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: [email protected].
  • 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: [email protected].
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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