Department of Oncologic Pathology, Mie University, Tsu, Japan.
Department of Oncologic Pathology, Mie University, Tsu, Japan,
Pharmacology. 2019;103(5-6):250-256. doi: 10.1159/000496831. Epub 2019 Feb 7.
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.
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.
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.
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.
吡非尼酮（PFD）是一种抗纤维化药物，用于治疗特发性肺纤维化，可诱导成纤维细胞的 G0/G1 细胞周期停滞。我们假设 PFD 诱导的 G0/G1 细胞周期停滞可能在其他类型的细胞中实现，包括癌细胞。在此，我们研究了 PFD 对体外胰腺癌细胞（PCCs）增殖的影响。
人皮肤成纤维细胞 ASF-4-1 细胞和人前列腺基质细胞（PrSC）用作成纤维细胞。PANC-1、MIA PaCa-2 和 BxPC-3 细胞用作人 PCCs。使用流式细胞仪分析细胞周期和细胞凋亡。
首先，我们证实 PFD 抑制 ASF-4-1 细胞和 PrSC 的细胞增殖并诱导 G0/G1 细胞周期停滞。在这些实验条件下，PFD 还抑制所有 PCCs 的细胞增殖并诱导 G0/G1 细胞周期停滞。在 PFD 处理的 PCCs 中，p21 的表达增加，但 CDK2 的表达没有明显降低。值得注意的是，PFD 并没有在 PCCs 中诱导明显的细胞凋亡。
这些结果表明，抗纤维化药物 PFD 通过诱导 G0/G1 细胞周期停滞可能对 PCCs 具有抗增殖作用。这表明 PFD 可能不仅针对胰腺癌细胞的肿瘤微环境中的成纤维细胞，而且还针对 PCCs。
