A Trifluoromethyl Quinazoline Compound Regulates the Epithelial-Mesenchymal Transition of Prostatic Hyperplasia Cells by Inhibiting the Secretion of TGF-β1 in Stromal Cells.

Benign prostatic hyperplasia (BPH) is a common disease in elderly men; its occurrence is closely related to the interaction between stromal cells and epithelial cells in the prostate. This article aims to explore the potential therapeutic effect and mechanism of a new trifluoromethyl quazoline compound (kzl054) on BPH. The results showed that kzl054 had inhibitory activity that limited the growth of prostate hyperplasia cells, BPH-1, and stromal cells, WPMY-1. It could also induce apoptosis of BPH-1 cells and arrest their cell cycle. animal experiment results showed that kzl054 could effectively reduce the volume and prostate index of mouse prostate hyperplasia tissues. Through the establishment of a co-culture system of BPH-1 and WPMY-1 cells, it was found that co-culture could induce EMT in BPH-1 cells. While kzl054 could affect the secretion of TGF-β1 by competitively binding to the colchicine binding site on β-tubulin and inhibiting the expression of β-tubulin, through inhibiting the secretion of TGF-β1 by stromal cells. This study has revealed that compound kzl054 inhibits the secretion of TGF-β1 by targeting the inhibition of microtubule polymerization and regulating the epithelial cell EMT, providing potential candidate molecules and mechanisms for the development of new drugs for the treatment of BPH.