Bokhari Amber A, Syed Viqar
Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
Department of Cell and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
J Cell Biochem. 2015 Aug;116(8):1797-805. doi: 10.1002/jcb.25138.
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.
转化生长因子-β（TGF-β）可调节细胞增殖、血管生成和转移，是上皮-间质转化（EMT）的诱导因子。癌细胞表现出激活的TGF-β/SMAD信号通路，抑制该通路是一种有吸引力的癌症治疗策略。中药黄芩（SB）和川贝母（FC）已被证明对癌症患者有益，但两种草药提取物发挥有益作用的机制尚不清楚。在本研究中，我们使用人子宫内膜癌细胞评估SB和FC对TGF-β信号通路成分的抗癌功效。用SB和FC处理癌细胞导致TGF-β亚型、TGF-β受体和SMADs的表达显著降低。两种草药均有效抑制基础状态和TGF-β1诱导的癌细胞增殖和侵袭，同时伴随着Snail、Slug、基质金属蛋白酶（MMPs）、αvβ3整合素、粘着斑激酶（FAK）和p-FAK表达的消除。TGF-βRI抑制剂可阻断TGF-β1诱导的细胞侵袭，并显著减弱SB和FC的抗肿瘤作用。这些结果表明，SB和FC通过下调TGF-β/SMAD信号通路来阻断子宫内膜癌的生长。
