Demethylzeylasteral (T-96) inhibits triple-negative breast cancer invasion by blocking the canonical and non-canonical TGF-β signaling pathways
Demethylzeylasteral (T-96) inhibits triple-negative breast cancer invasion by blocking the canonical and non-canonical TGF-β signaling pathways
复制标题
Demethylzeylasteral (T-96) 通过阻断经典和非经典 TGF-β 信号通路来抑制三阴性乳腺癌侵袭
DOI：
10.1007/s00210-019-01614-5
复制
发表时间：
2019-05-01
影响因子：
3.6
通讯作者：
Xu, Changliang
中科院分区：
文献类型：
--
作者：
Li, Liu;Ji, Yi;Xu, Changliang
炎症是人类肿瘤发展过程中的特征之一。已知在癌症发展过程中促进炎症的促炎细胞因子是转化生长因子-β (TGF-β)。另一方面，demethylzeylasteral (T-96) 是从雷公藤红 (Tripterygium wilfordii Hook F) 中分离出来的天然化合物，据报道其具有多种药理特性，包括抗炎和免疫抑制活性。我们研究了 T-96 对高度转移性乳腺癌细胞系 MDA-MB-231 的影响。通过划痕迁移测定评估细胞迁移，并通过 qPCR 和蛋白质印迹分析检查 T-96 影响的分子机制。我们还研究了 T-96 对 4T1 小鼠模型肺转移的抑制作用。 T-96 在体外和体内均抑制 TGF-β 诱导的迁移和上皮间质转化。这些结果表明，T-96 通过抑制经典和非经典 TGF-β 信号通路来抑制 MDA-MB-231 和 4T1 细胞的侵袭。
Inflammation is one of the characteristic features during the development of human tumors. A pro-inflammatory cytokine that is known to promote inflammation during cancer development is the transforming growth factor-beta (TGF-beta). On the other hand, demethylzeylasteral (T-96) is a natural compound isolated from Tripterygium wilfordii Hook F, which has been reported to have various pharmacological properties including anti-inflammatory and immunosuppressive activities. We investigated the effects of T-96 on the highly metastatic breast cancer cell line, MDA-MB-231. Cell migration was assessed by scratch-wound migration assay, and the molecular mechanisms underlying the effects of T-96 were examined by qPCR and Western blot analyses. We also investigated the suppression effects of T-96 on the pulmonary metastasis in the 4T1 mouse model. T-96 inhibited TGF-beta-induced migration and epithelial-mesenchymal transition both in vitro and in vivo. These results demonstrate that T-96 inhibited invasion of MDA-MB-231 and 4T1 cells via suppressing the canonical and non-canonical TGF-beta signaling pathways.