Abstract
TGF-β1 is an epithelial-mesenchymal transition (EMT)-inducing factor that is critical in tumor progression. However, whether the effect of TGF-β1 on breast cancer is through the EMT pathway remains to be determined, and drug development based on this mechanism needs to be improved. Results of this study showed that TGF-β1 dysregulation significantly correlated with the expression levels of EMT-associated markers and transcriptional factors. Exogenous expression of TGF-β1 promoted breast cancer cell metastasis and EMT progression. In addition, direct binding of baicalin to TGF-β1 caused its inactivation, which subsequently blocked signal transduction and inhibited breast cancer cell metastasis. In vivo experiment results further invalidated the inhibitory effect of baicalin on TGF-β1-induced tumor metastasis. These results suggest that baicalin, an active ingredient used in traditional Chinese medicine, exhibits a potential therapeutic effect on breast cancer metastasis by regulating TGF-β1-dependent EMT progression.
Highlights
Breast cancer is the most common cancer among women, affecting over 1.5 million women each year
These results suggest that baicalin, an active ingredient used in traditional Chinese medicine, exhibits a potential therapeutic effect on breast cancer metastasis by regulating TGF-β1-dependent epithelial-mesenchymal transition (EMT) progression
This study provides a deep understanding of the role of TGF-β1 in breast cancer progression and a basis for the development of potential therapeutic www.oncotarget.com substances in cancer based on TGF-β1-dependent EMT progression
Summary
Breast cancer is the most common cancer among women, affecting over 1.5 million women each year. It causes the greatest number of cancer-related deaths. In 2015, 570,000 women died from breast cancer, approximately 15% of all cancer deaths among women. Chemotherapy, radiation therapy, hormonal therapy, targeted therapies, and complementary and holistic medicine are among the different therapies used for the treatment of breast cancer [1–8], but their many side effects, such as chemotherapy-induced pain and immune system inhibition, limit their applications.Scutellaria baicalensis, a heat-clearing and detoxifying herb used in Chinese medicine, is widely used in China because of its anti-inflammatory, antimicrobial, antioxidative, anti-cancer, and cardiomyocyte-protective pharmacological properties [9–13]. Studies indicated that baicalin could induce the apoptosis and inhibit the metastases, invasion, migration, and fibrosis of various cancers, including breast cancer, through multiple pathways [14–18]. High doses of baicalin cause certain toxicities and induce kidney injury and fibrosis
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