Wogonoside inhibits invasion and migration through suppressing TRAF2/4 expression in breast cancer

Background: Twist1 is involved in tumor initiation and progression, which especially contributes to tumor invasion and metastasis. Wogonoside is the main in-vivo metabolite of wogonin, and it is also a natural product with potential treatment effects against Cancer.

Methods: In this study, we investigated the in-vitro anti-invasion and in-vivo anti-metastasis effects of wogonoside on breast Cancer cells and uncovered its underlying mechanism.

Results: The results showed that wogonoside could suppress the growth and metastasis of breast tumor in the orthotopic model of MDA-MB-231 cells. We found that wogonoside could reduce the overexpression of TNF-α, TRAF2 and TRAF4 in later stage of tumor, and improved tumor microenvironment. Therefore, TNF-α was utilized to induce metastases of breast Cancer cell in vitro. Wogonoside could inhibit invasion and migration in TNF-α-induced MDA-MB-231, MDA-MB-435, and BT-474 cells. Mechanically, wogonoside inactivated NF-κB signaling through decreasing the protein expression of TRAF2/4, which further inhibited Twist1 expression. Consequently, wogonoside could down-regulate MMP-9, MMP-2, vimentin and CD44v6 expression in TNF-α-induced MDA-MB-231 and MDA-MB-435 cells. Then, these findings were proved in TNF-α + TGF-β1-induced MCF7 cells.

Conclusions: Wogonoside might be a potential therapeutic agent for the treatment of tumor metastasis in breast Cancer.

NF-κB; TNF-α; TRAF2; TRAF4; Twist1; Wogonoside.