Tumor suppressor role of sFRP‑4 in hepatocellular carcinoma via the Wnt/β‑catenin signaling pathway.

Abstract

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.