Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian, P.R. China.
Fujian Medical University Cancer Hospital, Fujian, P.R. China.
Oncol Res. 2019 May 7;27(5):593-600. doi: 10.3727/096504017X15051723858706. Epub 2017 Sep 14.
Transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) of non-small cell lung cancer (NSCLC) may contribute to tumor metastasis. TGF-β1-induced EMT in H1975 cells (a human NSCLC cell line) resulted in the adoption of mesenchymal responses that were predominantly mediated via the TGF-β1-integrin signaling pathway. Ursolic acid has been previously reported to inhibit tumor growth and metastasis in several cancers. However, whether ursolic acid can attenuate TGF-β1-induced EMT in H1975 cells and its underlying mechanisms remain unknown. In this study, ursolic acid significantly attenuated the TGF-β1-induced decrease in E-cadherin level and elevated the level of N-cadherin. Furthermore, ursolic acid inhibited the mesenchymal-like responses in H1975 cells, including cell migration, invasion, and activity of matrix metallopeptidase (MMP)-2 and -9. Finally, our new findings provided evidence that ursolic acid could inhibit EMT in NSCLC through TGF-β1 signaling pathway-mediated integrin αVβ5 expression, and this might be the potential mechanism of resveratrol on the inhibition of invasion and metastases in NSCLC. We conclude that ursolic acid attenuated TGF-β1-induced EMT in H1975 cells and thus might be a promising therapeutic agent for treating NSCLC.
转化生长因子-β1（TGF-β1）诱导的非小细胞肺癌（NSCLC）上皮-间充质转化（EMT）可能有助于肿瘤转移。TGF-β1 诱导的 H1975 细胞（一种人 NSCLC 细胞系）中的 EMT 导致了间充质反应的出现，这些反应主要通过 TGF-β1-整合素信号通路介导。熊果酸先前已被报道可抑制几种癌症的肿瘤生长和转移。然而，熊果酸是否能减轻 H1975 细胞中 TGF-β1 诱导的 EMT 及其潜在机制尚不清楚。在本研究中，熊果酸显著减弱了 TGF-β1 诱导的 E-钙黏蛋白水平降低，并升高了 N-钙黏蛋白水平。此外，熊果酸抑制了 H1975 细胞中的间充质样反应，包括细胞迁移、侵袭以及基质金属蛋白酶（MMP）-2 和 -9 的活性。最后，我们的新发现提供了证据表明，熊果酸可通过 TGF-β1 信号通路介导的整合素 αVβ5 表达抑制 NSCLC 中的 EMT，这可能是白藜芦醇抑制 NSCLC 侵袭和转移的潜在机制。我们得出结论，熊果酸减弱了 H1975 细胞中 TGF-β1 诱导的 EMT，因此可能是治疗 NSCLC 的有前途的治疗剂。
