Pirfenidone, an Anti-Fibrotic Drug, Suppresses the Growth of Human Prostate Cancer Cells by Inducing G1 Cell Cycle Arrest
Pirfenidone, an Anti-Fibrotic Drug, Suppresses the Growth of Human Prostate Cancer Cells by Inducing G1 Cell Cycle Arrest
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DOI：
10.3390/jcm8010044
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Sugimura, Yoshiki
中科院分区：
文献类型：
--
作者：
Ishii, Kenichiro;Sasaki, Takeshi;Sugimura, Yoshiki
吡非尼酮（PFD）是一种抗纤维化药物，通过诱导成纤维细胞中的G（1）细胞周期停滞来治疗特发性肺纤维化。我们假设PFD可以诱导不同类型细胞（包括癌细胞）的G（1）细胞周期停滞。为了研究PFD处理对人前列腺癌（PCa）细胞生长的影响，我们使用了雄激素敏感的人PCa细胞系（LNCaP）及其亚系（雄激素低敏感的E9和F10细胞和雄激素不敏感的AIDL细胞），以及雄激素不敏感的人PCa细胞系（PC-3）。PFD处理抑制所有PCa细胞的生长。转化生长因子1分泌显着增加PFD处理的PCa细胞。在LNCaP和PC-3细胞中，PFD处理增加了G（0）/G（1）期细胞的数量，同时伴有S/G（2）期细胞数量的减少。PFD处理的LNCaP和PC-3细胞中CDK2蛋白表达明显降低，而P21蛋白表达仅在PFD处理的LNCaP细胞中增加。总之，PFD可能作为一种新的治疗药物，诱导G（1）细胞周期阻滞在人类前列腺癌细胞的雄激素敏感性无关。因此，在肿瘤微环境中，PFD可能不仅靶向成纤维细胞，而且靶向不同雄激素敏感性水平的异质性PCa细胞。
Pirfenidone (PFD) is an anti-fibrotic drug used to treat idiopathic pulmonary fibrosis by inducing G(1) cell cycle arrest in fibroblasts. We hypothesize that PFD can induce G(1) cell cycle arrest in different types of cells, including cancer cells. To investigate the effects of PFD treatment on the growth of human prostate cancer (PCa) cells, we used an androgen-sensitive human PCa cell line (LNCaP) and its sublines (androgen-low-sensitive E9 and F10 cells and androgen-insensitive AIDL cells), as well as an androgen-insensitive human PCa cell line (PC-3). PFD treatment suppressed the growth of all PCa cells. Transforming growth factor 1 secretion was significantly increased in PFD-treated PCa cells. In both LNCaP and PC-3 cells, PFD treatment increased the population of cells in the G(0)/G(1) phase, which was accompanied by a decrease in the S/G(2) cell population. CDK2 protein expression was clearly decreased in PFD-treated LNCaP and PC-3 cells, whereas p21 protein expression was increased in only PFD-treated LNCaP cells. In conclusion, PFD may serve as a novel therapeutic drug that induces G(1) cell cycle arrest in human PCa cells independently of androgen sensitivity. Thus, in the tumor microenvironment, PFD might target not only fibroblasts, but also heterogeneous PCa cells of varying androgen-sensitivity levels.