Anti-tumor activity of a recombinant soluble Fzd۷ decoy receptor in human gastric and colon cancer cells
Publish place: Iranian Journal of Basic Medical Sciences، Vol: 25، Issue: 2
Publish Year: 1401
نوع سند: مقاله ژورنالی
زبان: English
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JR_IJBMS-25-2_007
تاریخ نمایه سازی: 30 بهمن 1400
Abstract:
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.
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Authors
Nasim Hafezi
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Reza Valadan
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Hossein Asgarian-Omran
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
Abolghasem Ajami
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
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