Saringosterol acetate suppressed hepatocelluar carcinoma growth and metastasis in a zebrafish xenograft model

Abstract

Saringosterol acetate (SSA) can be isolated from an edible brown alga, Hizikia fusiforme. In this study, we developed an adult zebrafish human hepatocellular carcinoma (HCC) xenograft model to confirm our previous finding that SSA inhibitstumor growth and metastasis. The zebrafish is one of the most widely used model organisms for drug discovery, molecular genetics, and the screening of human diseases. Established Hep3B cells labeled with the fluorescent tracker CM-Dil werexenografted into the abdominal cavities of zebrafish once every three days for one month. Compared with the control group, the fish injected with Hep3B showed a significant increase in α-fetoprotein (AFP) and factors related to tumor growth and metastasis (IL-6, TNF-α, TGFβ, MMP2, and MMP9). Using the zebrafish xenograft model, we then showed that SSA affected survival rate, AFP production, and the levels of factors related to tumor growth and metastasis via the PI3K/AKT/mTOR and TGFβ/Smad pathways. In conclusion, this HCC model can be used for in vivo experiments to investigate the inhibition of cancer, and SSA isolated from H. fusiforme may be useful for the treatment of cancer.