Cadre Ward Two, General Hospital of The Central Theater Command of The People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
Department of Oncology, General Hospital of The Central Theater Command of The People's Liberation Army, Wuhan, Hubei 430070, P.R. China.
Mol Med Rep. 2021 May;23(5). doi: 10.3892/mmr.2021.11975. Epub 2021 Mar 24.
Hepatocellular carcinoma (HCC) is a malignant tumor located in the liver. Secreted frizzled‑related protein 4 (sFRP‑4) is associated with cancer occurrence, but the relationship between sFRP‑4 and HCC is not completely understood. The present study aimed to investigate the role and mechanism underlying sFRP‑4 in HCC. sFRP‑4 mRNA expression levels were determined via reverse transcription‑quantitative PCR and immunohistochemistry. The Cell Counting Kit‑8 assay was performed to evaluate HCCLM3 and Huh7 cell viability. Moreover, HCCLM3 and Huh7 cell proliferation were assessed using the BrdU ELISA assay kit, and cell apoptosis was measured via flow cytometry. Western blotting was conducted to measure β‑catenin and GSK‑3β protein expression levels. The results demonstrated that sFRP‑4 expression was significantly downregulated in HCC tissues and cells compared with adjacent healthy tissues and MIHA cells, respectively. Moreover, the results indicated that compared with the control group, sFRP‑4 overexpression inhibited HCC cell viability and proliferation, and accelerated HCC cell apoptosis. Furthermore, the results suggested that sFRP‑4 inhibited the Wnt/β‑catenin signaling pathway by upregulating GSK‑3β expression and downregulating β‑catenin expression, thus restraining the malignant behavior of HCC cells. In conclusion, the present study indicated that sFRP‑4 served a tumor suppressor role in HCC cells by restraining the Wnt/β‑catenin signaling pathway.
肝细胞癌 (HCC) 是一种位于肝脏的恶性肿瘤。分泌卷曲相关蛋白 4 (sFRP-4) 与癌症的发生有关，但 sFRP-4 与 HCC 之间的关系尚不完全清楚。本研究旨在探讨 sFRP-4 在 HCC 中的作用及其机制。通过逆转录-定量 PCR 和免疫组织化学检测 sFRP-4 mRNA 表达水平。采用细胞计数试剂盒-8 检测 HCCLM3 和 Huh7 细胞活力。此外，使用 BrdU ELISA 检测试剂盒评估 HCCLM3 和 Huh7 细胞增殖，通过流式细胞术检测细胞凋亡。采用 Western blot 检测β-连环蛋白和 GSK-3β 蛋白表达水平。结果表明，与相邻健康组织和 MIHA 细胞相比，sFRP-4 在 HCC 组织和细胞中的表达明显下调。此外，与对照组相比，sFRP-4 过表达抑制 HCC 细胞活力和增殖，并加速 HCC 细胞凋亡。进一步研究表明，sFRP-4 通过上调 GSK-3β 表达和下调 β-连环蛋白表达抑制 Wnt/β-连环蛋白信号通路，从而抑制 HCC 细胞的恶性行为。综上所述，本研究表明 sFRP-4 通过抑制 Wnt/β-连环蛋白信号通路在 HCC 细胞中发挥肿瘤抑制作用。
