Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.
Hangzhou Normal University School of Medicine, Hangzhou, 311121, China.
Cell Death Dis. 2018 Apr 1;9(4):431. doi: 10.1038/s41419-018-0415-2.
The activation of androgen receptor (AR) signaling plays an essential role in both prostate stromal cells and epithelial cells during the development of benign prostatic hyperplasia (BPH). Here we demonstrated that androgen ablation after 5α-reductase inhibitor (5-ARI) treatment induced autophagy in prostate stromal fibroblasts inhibiting cell apoptosis. In addition, we found that ATG9A expression was increased after androgen ablation, which facilitated autophagic flux development. Knockdown of ATG9A not only inhibited autophagy notably in prostate stromal fibroblasts, but also reduced the volumes of prostate stromal fibroblast and epithelial cell recombinant grafts in nude mice. In conclusion, our findings suggested that ATG9A upregulation after long-term 5-ARI treatment constitutes a possible mechanism of BPH progression. Thus, combined treatment with 5-ARI and autophagy inhibitory agents would reduce the risk of BPH progression.
雄激素受体（AR）信号的激活在良性前列腺增生（BPH）的发展过程中，无论是在前列腺基质细胞还是上皮细胞中都发挥着重要作用。在这里，我们证明了 5α-还原酶抑制剂（5-ARI）治疗后雄激素的去除会诱导前列腺基质成纤维细胞中的自噬，从而抑制细胞凋亡。此外，我们发现雄激素去除后 ATG9A 的表达增加，这促进了自噬流的发展。ATG9A 的敲低不仅显著抑制了前列腺基质成纤维细胞中的自噬，而且还减少了裸鼠中前列腺基质成纤维细胞和上皮细胞重组移植物的体积。总之，我们的研究结果表明，长期 5-ARI 治疗后 ATG9A 的上调可能是 BPH 进展的一种机制。因此，联合使用 5-ARI 和自噬抑制剂的治疗方法可能会降低 BPH 进展的风险。
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