Antifibrotic Agent Pirfenidone Suppresses Proliferation of Human Pancreatic Cancer Cells by Inducing G0/G1 Cell Cycle Arrest
Antifibrotic Agent Pirfenidone Suppresses Proliferation of Human Pancreatic Cancer Cells by Inducing G0/G1 Cell Cycle Arrest
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DOI：
10.1159/000496831
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发表时间：
2019-02
期刊：
影响因子：
3.1
通讯作者：
Eri Usugi;K. Ishii;Y. Hirokawa;Kazuki Kanayama;Chise Matsuda;K. Uchida;T. Shiraishi;Masatoshi Watanabe
中科院分区：
文献类型：
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作者：
Eri Usugi;K. Ishii;Y. Hirokawa;Kazuki Kanayama;Chise Matsuda;K. Uchida;T. Shiraishi;Masatoshi Watanabe
背景：吡非尼酮（PFD）是一种用于治疗特发性肺纤维化的抗纤维化药物，可诱导成纤维细胞G0/G1细胞周期阻滞。我们假设pfd诱导的G0/G1细胞周期阻滞可能在其他类型的细胞中实现，包括癌细胞。我们在体外研究了PFD对胰腺癌细胞（PCCs）增殖的影响。方法：以人皮肤成纤维细胞ASF-4-1细胞和人前列腺基质细胞（PrSC）为成纤维细胞。PANC-1、MIA PaCa-2和BxPC-3细胞作为人PCCs。流式细胞仪分析细胞周期和凋亡情况。结果：首先，我们证实了PFD抑制ASF-4-1细胞和PrSC的细胞增殖，诱导G0/G1细胞周期阻滞。在这些实验条件下，PFD还抑制了所有PCCs的细胞增殖并诱导G0/G1细胞周期阻滞。在pfd处理的PCCs中，p21的表达增加，而CDK2的表达没有明显下降。值得注意的是，PFD在PCCs中没有引起明显的细胞凋亡。结论：抗纤维化药物PFD可能通过诱导G0/G1细胞周期阻滞对PCCs具有抗增殖作用。这表明PFD不仅可以靶向成纤维细胞，还可以靶向胰腺癌肿瘤微环境中的PCCs。
Background: Pirfenidone (PFD), which is an antifibrotic agent used for treatment of idiopathic pulmonary fibrosis, induces G0/G1 cell cycle arrest in fibroblasts. We hypothesized that PFD-induced G0/G1 cell cycle arrest might be achieved in other types of cells, including cancer cells. Here we investigated the effects of PFD on the proliferation of pancreatic cancer cells (PCCs) in vitro. Method: Human skin fibroblasts ASF-4-1 cells and human prostate stromal cells (PrSC) were used as fibroblasts. PANC-1, MIA PaCa-2, and BxPC-3 cells were used as human PCCs. Cell cycle and apoptosis were analyzed using flow cytometer. Results: First, we confirmed that PFD suppressed cell proliferation of ASF-4-1 cells and PrSC and induced G0/G1 cell cycle arrest. Under these experimental conditions, PFD also suppressed cell proliferation and induced G0/G1 cell cycle arrest in all PCCs. In PFD-treated PCCs, expression of p21 was increased but that of CDK2 was not clearly decreased. Of note, PFD did not induce significant apoptosis among PCCs. Conclusions: These results demonstrated that the antifibrotic agent PFD might have antiproliferative effects on PCCs by inducing G0/G1 cell cycle arrest. This suggests that PFD may target not only fibroblasts but also PCCs in the tumor microenvironment of pancreatic cancer.