Inhibition of Transforming Growth Factor-β (TGF-β) Signaling by Scutellaria baicalensis and Fritillaria cirrhosa Extracts in Endometrial Cancer.

Transforming growth factor-β (TGF-β), regulates cell proliferation, angiogenesis, metastasis, and is an inducer of epithelial-mesenchymal transition (EMT). Cancer cells exhibit activated TGF-β/SMAD signaling pathway and its inhibition is an attractive strategy for cancer treatment. The Chinese Herbs Scutellaria baicalensis (SB) and Fritillaria cirrhosa (FC) have been shown to be beneficial to cancer patients, but the mechanisms by which the extracts of two herbs elicit the beneficial effects are unclear. In this study, we have used human endometrial cancer cells to assess the anticancer efficacy of SB and FC on TGF-β signaling pathway components. SB and FC treatment of cancer cells resulted in a significant decrease in expression of TGF-β isoforms, TGF-β receptors, and SMADs. Both herbs effectively inhibited basal and TGF-β1-induced cancer cell proliferation and invasion, which was accompanied with abrogation of Snail, Slug, matrix metalloproteinases (MMPs), αvβ3 integrin, focal adhesion kinase (FAK), and p-FAK expression. An inhibitor of TGF-βRI blocked TGF-β1-induced cell invasion and significantly diminished antitumor effects of SB and FC. These results suggest that SB and FC block endometrial cancer growth by downregulating TGF-β/SMAD signaling pathway.