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Updated: Feb 25, 2026
Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Wogonoside inhibits invasion and migration through suppressing TRAF2/4 expression in breast cancer
Yuyuan Yao1, Kai Zhao1, Zhou Yu1
1State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.
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.
Insights
Wogonoside effectively suppresses breast cancer metastasis by inhibiting invasion and migration. It targets the NF-κB signaling pathway, reducing key proteins involved in tumor spread and improving the tumor microenvironment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Twist1 plays a crucial role in tumor initiation, invasion, and metastasis.
- Wogonoside, a wogonin metabolite, exhibits potential anti-cancer properties.
Purpose of the Study:
- To investigate the in-vitro anti-invasion and in-vivo anti-metastasis effects of wogonoside on breast cancer.
- To elucidate the underlying molecular mechanisms of wogonoside's action.
Main Methods:
- Utilized orthotopic breast tumor models (MDA-MB-231 cells) and in-vitro cell culture systems.
- Investigated the effects of wogonoside on TNF-α, TRAF2, TRAF4, NF-κB signaling, Twist1, and downstream metastasis-related genes (MMP-9, MMP-2, vimentin, CD44v6).
- Validated findings in TNF-α and TNF-α + TGF-β1 induced breast cancer cell lines (MDA-MB-231, MDA-MB-435, BT-474, MCF7).
Main Results:
- Wogonoside suppressed breast tumor growth and metastasis in vivo.
- Wogonoside reduced TNF-α, TRAF2, and TRAF4 overexpression, improving the tumor microenvironment.
- Wogonoside inhibited invasion and migration in TNF-α-induced breast cancer cells by inactivating NF-κB signaling and down-regulating Twist1, MMP-9, MMP-2, vimentin, and CD44v6 expression.
Conclusions:
- Wogonoside demonstrates significant anti-metastatic potential in breast cancer.
- Wogonoside may serve as a promising therapeutic agent for treating breast cancer metastasis.
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