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

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.