Anti-proliferative activities of finasteride in benign prostate epithelial cells require stromal fibroblasts and c-Jun gene

Abstract

This study aimed to identify the role of mouse fibroblast-mediated c-Jun and IGF-1 signaling in the therapeutic effect of finasteride on benign prostatic epithelial cells. BPH-1 cells, alone or with fibroblasts (c-Jun+/+ or c-Jun-/-), were implanted subcutaneously in male nude mice who were then treated with finasteride. The degrees of cell proliferation, apoptosis, and sizes of the xenografts were determined. BPH-1 cells were grown alone or co-cultured with mouse fibroblasts in the presence of finasteride and the level of IGF-1 secreted into the medium by the fibroblasts was determined. The proliferation-associated signaling pathway in BPH-1 cells was also evaluated. Fibroblasts and c-Jun promoted xenograft growth, stimulated Ki-67 expression, and inhibited BPH-1 apoptosis. Finasteride did not induce the shrinkage of xenografts in the combined-grafted groups despite repressing Ki-67 expression and inducing cell apoptosis. The addition of c-Jun-/- fibroblasts did not promote xenograft growth. In the absence of c-Jun and fibroblasts, finasteride did not alter xenograft growth, Ki-67 expression, or cell apoptosis. The in vitro results demonstrated that when BPH-1 cells were grown in monoculture, treatment with finasteride did not induce cell death and stimulated the expression of pro-proliferative signaling molecules, while in the presence of fibroblasts containing c-Jun, finasteride treatment repressed epithelial cell proliferation, the level of IGF-1 in the medium, and the activation of downstream pro-proliferative signaling pathways. Taken together, our results suggest that fibroblasts, c-Jun, and IGF-1 play key roles in mediating stromal-epithelial interactions that are required for the therapeutic effects of finasteride in benign prostate epithelial cells.

Qianlongtong Inhibits Proliferation and Induces Apoptosis of Hyperplastic Prostate Cells

“…The final results favor apoptosis. This apoptosis-inducing effect has also been observed when finasteride was used in culture, although finasteride also presented an antiproliferative effect on prostatic cells ( Wang et al, 2017 ).…”

A Network Pharmacology Approach and Molecular Docking Technology to Uncover the Potential Molecular Mechanism of Astragalus -Scorpion on Prostate Cancer

“…JUN is the rst found carcinogenic transcription factor. c-JUN is an AR co-activator, which stimulates AR transactivation by mediating receptor dimerization and subsequent DNA binding, and plays a key role in the proliferative function of broblasts and the anti-proliferative activity of nasteride on epithelial cells [28]. IL6, a glycogen composed of 184 amino acids, is a pluripotent cytokine that affects tumor cell activity and plays an important role in immune response and in ammation [29,30].…”

Crosstalk between androgen and Wnt/β-catenin leads to changes of wool density in FGF5-knockout sheep

“…For further verification of the crosstalk between androgen and Wnt/β-catenin pathway, we added DHT, finasteride, and DMSO in the culture medium of DPCs to detect the expression of related genes. We explored the optimal concentration of DHT and finasteride in DPCs based on relevant reports 42 ( Supplementary Fig. S5).…”