The intriguing role of fibroblasts and c-Jun in the chemopreventive and therapeutic effect of finasteride on xenograft models of prostate cancer  

作　　者：Yi-Nong Niu Kai Wang Song Jin Dong-Dong Fan Ming-Shuai Wang Nian-Zeng Xing Shu-Jie Xia 

机构地区：[1]Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China [2]Weifang Hospital of Traditional Chinese Medicine, Weifang, China [3]Department of Urology, Shanghai First Hospital, Jiao Tong University, Shanghai, China

出　　处：《Asian Journal of Andrology》2016年第6期913-919,共7页亚洲男性学杂志（英文版）

摘　　要：In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer （PCa） while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP （PC3） cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERKI/2 were evaluated. In LNCaP （PC3） mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, flbroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERKI/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERKI/2 were noted in the presence of c-Jun-I- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride＇s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer （PCa） while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP （PC3） cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERKI/2 were evaluated. In LNCaP （PC3） mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, flbroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERKI/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERKI/2 were noted in the presence of c-Jun-I- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride＇s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

关 键 词：CHEMOPREVENTION C-JUN FIBROBLASTS FINASTERIDE mouse model prostate cancer 

分 类 号：R[医药卫生]