Double-stranded RNA-activated protein kinase R (PKR) is highly expressed in colorectal cancer (CRC). However, the role of PKR in CRC remains unclear. The aim of this study was to clarify whether C16 (a PKR inhibitor) exhibits antitumor effects and to identify its target pathway in CRC. We evaluated the effects of C16 on CRC cell lines using the MTS assay. Enrichment analysis was performed to identify the target pathway of C16. The cell cycle was analyzed using flow cytometry. Finally, we used immunohistochemistry to examine human CRC specimens. C16 suppressed the proliferation of CRC cells. Gene Ontology (GO) analysis revealed that the cell cycle-related GO category was substantially enriched in CRC cells treated with C16. C16 treatment resulted in G1 arrest and increased p21 protein and mRNA expression. Moreover, p21 expression was associated with CRC development as observed using immunohistochemical analysis of human CRC tissues. C16 upregulates p21 expression in CRC cells to regulate cell cycle and suppress tumor growth. Thus, PKR inhibitors may serve as a new treatment option for patients with CRC.

双链 RNA 激活蛋白激酶 R (PKR) 在结直肠癌 (CRC) 中高表达。然而，PKR 在 CRC 中的作用仍不清楚。本研究的目的是阐明 C16（一种 PKR 抑制剂）是否具有抗肿瘤作用，并确定其在 CRC 中的靶通路。我们使用 MTS 测定评估了 C16 对 CRC 细胞系的影响。进行富集分析以确定 C16 的靶途径。使用流式细胞术分析细胞周期。最后，我们使用免疫组织化学检查人类结直肠癌标本。 C16 抑制 CRC 细胞的增殖。基因本体 (GO) 分析显示，在用 C16 处理的 CRC 细胞中，细胞周期相关的 GO 类别显着富集。 C16 处理导致 G1 期停滞并增加 p21 蛋白和 mRNA 表达。此外，利用人类结直肠癌组织的免疫组织化学分析观察到，p21 表达与结直肠癌的发展相关。 C16 上调 CRC 细胞中 p21 的表达，从而调节细胞周期并抑制肿瘤生长。因此，PKR抑制剂可能成为结直肠癌患者的新治疗选择。