Department of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Department of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Toon, Ehime, Japan.
Sci Rep. 2020 Mar 20;10(1):5133. doi: 10.1038/s41598-020-61579-x.
The therapeutic effects of C16, which is an inhibitor of RNA-dependent protein kinase (PKR), on growth of hepatocellular carcinoma (HCC) cells and tumor progression in vitro and in vivo were evaluated. Huh7 cells, a human HCC cell line, were used. The effects of C16 on cell viability were evaluated with the MTT assay, and real-time RT-PCR was performed. Huh7 cells were grafted into immunodeficient mice, and the in vivo effects of C16 on tumorigenesis were examined. C16 suppressed proliferation of HCC cells in a dose-dependent manner in vitro. Mouse models with xenograft transplantation showed that the inhibitor suppressed the growth of HCC cells in vivo. Moreover, C16 decreased angiogenesis in HCC tissue in the xenograft model. Consistent with these results in mice, transcript levels of vascular endothelial growth factor-A and factor-B, platelet-derived growth factor-A and factor-B, fibroblast growth factor-2, epidermal growth factor, and hepatocyte growth factor, which are angiogenesis-related growth factors, were significantly decreased by C16 in vitro. In conclusion, the PKR inhibitor C16 blocked tumor cell growth and angiogenesis via a decrease in mRNA levels of several growth factors. C16 may be useful in the treatment of HCC.
评估了 RNA 依赖性蛋白激酶（PKR）抑制剂 C16 对肝癌（HCC）细胞体外和体内生长及肿瘤进展的治疗效果。使用了人肝癌细胞系 Huh7 细胞。通过 MTT 检测法评估 C16 对细胞活力的影响，并进行实时 RT-PCR。将 Huh7 细胞移植到免疫缺陷小鼠中，检查 C16 对肿瘤发生的体内影响。C16 体外呈剂量依赖性抑制 HCC 细胞增殖。异种移植移植模型的小鼠表明，该抑制剂在体内抑制 HCC 细胞的生长。此外，C16 减少了异种移植模型中 HCC 组织中的血管生成。与这些在小鼠中的结果一致，体外 C16 显著降低了与血管生成相关的生长因子血管内皮生长因子-A 和因子-B、血小板衍生生长因子-A 和因子-B、成纤维细胞生长因子-2、表皮生长因子和肝细胞生长因子的转录水平。综上所述，PKR 抑制剂 C16 通过降低几种生长因子的 mRNA 水平来阻断肿瘤细胞生长和血管生成。C16 可能对 HCC 的治疗有用。
