| Background/Objectives: Silencing of Wnt antagonists with aberrant activation of Wnt signaling plays an important role in the solid carcinogenesis as well as leukemia. Initiation of Wnt canonical signaling is modulated by soluble Wnt antagonists, including soluble frizzled related proteins (sFRPs) and Wnt inhibitory factor-1 (Wif1). Exogenous expression of Wnt antagonists Wif-1 could regulate Wnt signaling and may exert antitumor activity. Evidences have been shown that combination of protein with IgG-Fc fragment can prolong the circulating half-life of the protein in vivo. Therefore, in this study we have constructed fusion proteins of Wif1 with Fc fragment of IgG1 and explored antitumoral activity in vitro conditions.Methods: Human Wif1 cDNA was cloned and were fused with Fc region of human IgG1 to make Wif1-Fe. The recombinant adenoviral vector carrying Wif1-Fc driven by CMV promoter were constructed, respectively. The recombinant fusion proteins were purified with affinity Hi-tap protein A column.Results: Our data showed that infection of solid tumor cells with Ad-Wif1-Fc could result in the expression and correct conformation of Wif1-Fc fusion proteins, Wif1-Fc had no cytopathic effect on normal cells. Inhibition of Wnt signaling was documented by downregulation of cyclin D, E2F1 and C-myc in leukemia cells after incubated with Wif1-Fc. TOP flash and FOP flash reporter assay further confirmed the decrease of wnt signaling in lymphoblastic cell in the recombinant protein treated groups. Apototic rate induced by Wif1-Fc alone was low, but the antitumor effect was greater and more pronounced by the combined use of Wif1-Fc and Homoharringtonine (HHT).Conclusion: Taken together, our dada indicated that expression of Wnt antagonists Wif1-Fc could inhibit Wnt signaling and induce antitumor activity via induction of tumor cells apoptosis. Our results suggested Wif1-Fc might be used as an adjuvant therapy for leukemia. But the underlied mechanism needs to be further explored.
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