Anti-tumor activity of a recombinant soluble Fzd۷ decoy receptor in human gastric and colon cancer cells

Objective(s): Frizzled-۷, the most common receptor of the Wnt signaling pathway, was significantly over-expressed in gastric (GC) and colorectal (CRC) cancers and stimulated tumorigenesis. The extracellular domain of Fzd۷ (sFzd۷) as a decoy receptor, could competitively bound with ligands and antagonize the interaction between Fzd۷ receptors and Wnt ligands. Materials and Methods: We expressed and purified the extracellular region of Fzd۷ including cysteine-rich domain (۳۳ aa–۱۸۵ aa) from Escherichia coli by chromatography. The effect of sFzd۷ was evaluated on AGS gastric and SW۴۸۰ colon cancer cell lines expressing high levels of Fzd۷ receptor. Accordingly, cell viability and apoptosis were measured using MTT and flow cytometry assays, respectively. Real-Time PCR determined the relative expression of the β-catenin and cyclin-D۱ genes. Results: After three days of treatment with sFzd۷, the viability of AGS and SW۴۸۰ cell lines was decreased in a dose-dependent manner. In addition, sFzd۷ at concentrations of ۱۰ and ۲۰ ug/ml increased the rate of apoptosis. Especially at the concentration of ۲۰ ug/ml, the apoptosis rate was remarkably high in AGS (P-value= ۰.۰۰۳) and SW۴۸۰ cells (P-value= ۰.۰۰۰۷). Finally, the expressions of β-catenin (P-value= ۰.۰۱) and cyclin-D۱ (P-value= ۰.۰۲) were obviously decreased in SW۴۸۰ cells. The same results were obtained in AGS cells, although not statistically significant. Conclusion: sFzd۷ decoy receptor inhibits tumor cell progression by attenuating the Wnt pathway through inhibiting Fzd۷ receptors and Wnt ligand interaction. Hence, sFzd۷ can be proposed as a candidate therapy for GC and CRC cells with high levels of Fzd۷ expression.

کلیدواژه ها:

Anti-tumor activity ، Colon cancer ، Decoy receptor ، Gastric cancer ، Recombinant protein ، Soluble Fzd۷