Omega-3 polyunsaturated fatty acid inhibits the malignant progression of hepatocarcinoma by inhibiting the Wnt/β-catenin pathway

Eur Rev Med Pharmacol Sci. 2018 Jul;22(14):4500-4508. doi: 10.26355/eurrev_201807_15504.


Objective: Omega-3 polyunsaturated fatty acid (ω-3 PUFA) has been found to possess anti-cancer potential in previous studies. However, the underlying mechanism of ω-3 PUFA in protecting hepatocarcinoma has not been fully elucidated. This study aims to explore the function of ω-3 PUFA in the development of hepatocarcinoma and its potential mechanism.

Patients and methods: In this study, human hepatocarcinoma cell line Hep G2 was treated with ω-3 PUFA. Cell counting kit-8 (CCK-8) and cell cloning assay were applied to detect the proliferation of Hep G2 cells. In addition, flow cytometry was performed to analyze the cell cycle and apoptosis rate. At the same time, the effect of ω-3 PUFA on invasion and metastasis of hepatocarcinoma cells were analyzed by transwell assay. Moreover, protein levels of key factors in Wnt/β-catenin pathway were detected by Western blot.

Results: Cell proliferation of Hep G2 cells was decreased after ω-3 PUFA treatment in a time- and dose-dependent manner. CCK-8 assay showed that the IC50 value was 12.8 ± 0.67 μmol/L, 8.8 ± 0.43 μmol/L and 4.6 ± 0.42 μmol/L after ω-3 PUFA treatment for 24 h, 48 h and 72 h, respectively. Besides, ratio of Hep G2 cells blocked at G2/M phase after ω-3 PUFA treatment (5 μmol/L, 10 μmol/L and 20 μmol/L) was increased in a dose-dependent manner (p<0.05). Meanwhile, ω-3 PUFA could increase cell apoptosis (p<0.05) and inhibit cell proliferation. In addition, ω-3 PUFA reduced protein expressions of total, cytoplasmic and nuclear β-catenin in Hep G2 cells, indicating that the Wnt/β-catenin pathway is inhibited. Decreased expression levels of Dvl-2, Dvl-3, GSK-3β (p-ser9), c-myc and survivin, and increased expression levels of GSK-3 (p-tyr216) and Axin-2 were observed in Hep G2 cells treated with ω-3 PUFA, but no significant alteration in total GSK-3β protein level was observed (p>0.05).

Conclusions: Omega-3 PUFA regulates the malignant progression of hepatocarcinoma by inhibiting proliferation and promoting apoptosis of hepatocarcinoma cells via Wnt/β-catenin signaling pathway.

MeSH terms

  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation / drug effects
  • Disease Progression
  • Drug Screening Assays, Antitumor
  • Fatty Acids, Omega-3 / administration & dosage*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Wnt Signaling Pathway / drug effects*


  • Fatty Acids, Omega-3