Fig 1.
Expression of AR, 5-AR1 and 5-AR2 in mouse fibroblast and BPH-1 cells.
(A) mRNA transcription of AR and 5-AR in BPH-1 cells. Low level of AR mRNA, high level of 5-AR1 mRNA and negative 5-AR2 mRNA were detected in BPH-1 cells. (B) mRNA transcription of AR and 5-AR in mouse fibroblasts. A small quantity of AR mRNA and 5-AR2 mRNA, high level of 5-AR1 mRNA were found in mouse fibroblasts.
Fig 2.
Cell proliferation and apoptosis in vitro and in xenografts of BPH-1-fibroblast-combined-grafted model.
(A) Cell proliferation of BPH-1 cells in mono-culture. High concentrations of finasteride did not inhibit cell proliferation in mono-culture. (B) Cell proliferation of BPH-1 cells co-cultured with wild-type fibroblasts or c-Jun-/- fibroblasts. In the presence of fibroblasts, finasteride repressed cell proliferation by 30% (p = 0.003). (C&D) Growth curve of xenografts in the BPH-1-fibroblast-combined-grafted model. Compared with the BPH-1 mono-grafted group, wild-type fibroblasts (c-Jun+/+) promoted xenograft growth whereas c-Jun-/- fibroblasts did not stimulate xenograft growth. Finasteride did not have a significant impact on xenograft growth in the presence or absence of fibroblasts in limited 5-week experimental period.
Fig 3.
Cell proliferation and apoptosis in xenograft tissues.
(A) Immunostaining of Ki-67, CK, vimentin and TUNEL in xenografted tissues. (B) Fibroblasts and c-Jun promoted the expression of Ki-67 in BPH-1 cells. Finasteride decreased the ratio of Ki-67-positive cells in epithelial cells in BPH-1-fibroblasts (c-Jun+/+) combined-grafted group. (C) Fibroblasts and c-Jun repressed the ratio of apoptotic BPH-1 cells, whereas finasteride promoted cell apoptosis in the presence of fibroblasts.
Fig 4.
The therapeutic effect of finasteride on fibroblasts.
(A) Finasteride induced cell death of fibroblasts. (B) Finasteride repressed the transcription of IGF-1 mRNA in fibroblasts in epithelia-fibroblasts co-culture system. (C) The level of IGF-1 protein in the medium of co-culture system was decreased in the presence of finasteride.
Fig 5.
The effect of finasteride on proliferation-associated signaling pathway in BPH-1 in mono-culture or co-culture with fibroblasts.
(A) Finasteride stimulated the expression of p-AKT, p-ERK1/2, cyclin D1 and cyclin D3 in a concentration-dependent manner in BPH-1 mono-culture. (B) Finasteride repressed the expression of p-AKT, p-ERK1/2 and cyclin D1 in BPH-1 cells when co-cultured with fibroblasts. The inhibiting effect of finasteride on downstream proliferation-associated signaling pathway was compromised by c-Jun knockout in fibroblasts.