ZFIN ID: ZDB-PUB-191106-11
Omega-3 polyunsaturated fatty acids suppress metastatic features of human cholangiocarcinoma cells by suppressing twist
Lin, C.R., Chu, T.M., Luo, A., Huang, S.J., Chou, H.Y., Lu, M.W., Wu, J.L.
Date: 2019
Source: The Journal of Nutritional Biochemistry   74: 108245 (Journal)
Registered Authors: Wu, Jen-Leih
Keywords: Cholangiocarcinoma, DHA, EPA, Fish oil, Metastasis, PUFA, Zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Bile Duct Neoplasms/diet therapy*
  • Bile Duct Neoplasms/pathology
  • Cell Cycle Checkpoints/drug effects
  • Cell Cycle Checkpoints/genetics
  • Cell Line, Tumor
  • Cell Movement/drug effects
  • Cell Movement/genetics
  • Cell Proliferation/drug effects
  • Cell Survival/drug effects
  • Cholangiocarcinoma/diet therapy*
  • Cholangiocarcinoma/pathology
  • Fatty Acids, Omega-3/chemistry
  • Fatty Acids, Omega-3/pharmacology*
  • Fish Oils/chemistry
  • Fish Oils/pharmacology
  • Gene Expression Regulation, Neoplastic/drug effects
  • Humans
  • Larva/drug effects
  • Nuclear Proteins/genetics*
  • Twist-Related Protein 1/genetics*
  • Xenograft Model Antitumor Assays
  • Zebrafish/genetics
PubMed: 31678746 Full text @ J. Nutr. Biochem.
Cholangiocarcinoma (CCA) is a highly malignant cancer of the bile duct, which has a five-year survival rate less than 5% due to a high metastasis rate and lack of therapeutic options. Although omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to inhibit the proliferation of CCA cells, the effects on CCA metastasis have not been previously reported. In this study, we first assessed the proliferation, migration and invasion effects of n-3 PUFA-based fish oil on human CCA cells. Then, we investigated PUFA effects on metastasis in vivo by xenografting CCA cells into zebrafish larvae that overexpress a critical n-3 PUFA synthesis gene, Δ6 fatty acid desaturase. The results indicated that n-3 PUFA-based fish oil suppresses CCA cell growth, potentially by blocking the cell cycle at G2/M phase, and it inhibits migration and invasion potential with coincident downregulation of migration-related genes. Furthermore, zebrafish endogenous n-3 PUFAs appear to suppress CCA metastasis by inhibiting the expression of twist, a key regulator of tumor metastasis. Interestingly, only long chain n-3 PUFAs could inhibit the expression of twist in CCA cells. Together, our results suggest that n-3 PUFAs, especially DHA, may inhibit proliferation and metastasis of CCA cells by inhibiting the expression of twist.