Hei Bo, Liu Ru-En, Li Meihua
Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Jiangxi, China.
Department of Neurosurgery, Peking University People's Hospital, Peking University, Beijing, China.
Heliyon. 2024 Mar 7;10(6):e27722. doi: 10.1016/j.heliyon.2024.e27722. eCollection 2024 Mar 30.
Found in many fruits and plants, Ursolic acid (UA), a pentacyclic triterpene that occurs naturally, is recognized for its anti-cancer effects, especially in combating glioblastoma. However, the intricate molecular mechanisms underpinning its anti-tumor actions are still not fully understood, despite the recognition of these effects. By examining the functions of epithelial-mesenchymal transition (EMT) and angiogenesis, crucial for glioblastoma progression, and their regulation through Transforming Growth Factor Beta (TGFβ) - a key marker for glioblastoma, our research aims to fill this knowledge gap. This study explores how ursolic acid can block the progression of glioblastoma by precisely targeting TGFβ-triggered EMT and angiogenesis. The findings show that UA successfully blocks the spread, movement, and invasion of glioblastoma cells. Accompanying this, there is a significant reduction in the expression of TGFβ and crucial EMT indicators like snail and vimentin. Furthermore, UA shows a reduction in angiogenesis that depends on the dosage, highlighted by decreased vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells (HUVECs). Interestingly, increased TGFβ expression in U87 and U251 glioblastoma cell lines was found to weaken UA's anti-tumor properties, shedding more light on TGFβ's critical function in glioblastoma's pathology. Supporting these laboratory results, UA also showed considerable inhibition of tumor growth in a glioblastoma xenograft mouse model. Overall, our research emphasizes Ursolic acid's promise as a new treatment for glioblastoma and clarifies its action mechanism, mainly by inhibiting TGFβ signaling and thereby EMT and angiogenesis.
熊果酸（UA）是一种天然存在的五环三萜，存在于许多水果和植物中，因其抗癌作用而闻名，尤其是在对抗胶质母细胞瘤方面。然而，尽管人们已经认识到其抗癌作用，但其抗肿瘤作用背后复杂的分子机制仍未完全了解。通过研究上皮-间质转化（EMT）和血管生成的功能（这两者对胶质母细胞瘤的进展至关重要）以及它们通过转化生长因子β（TGFβ）的调控（TGFβ是胶质母细胞瘤的关键标志物），我们的研究旨在填补这一知识空白。本研究探讨了熊果酸如何通过精确靶向TGFβ触发的EMT和血管生成来阻断胶质母细胞瘤的进展。研究结果表明，UA成功地阻断了胶质母细胞瘤细胞的扩散、移动和侵袭。与此同时，TGFβ以及关键的EMT指标如蜗牛蛋白和波形蛋白的表达显著降低。此外，UA显示出血管生成的减少，这取决于剂量，人脐静脉内皮细胞（HUVECs）中血管内皮生长因子（VEGF）的减少突出了这一点。有趣的是，在U87和U251胶质母细胞瘤细胞系中发现TGFβ表达增加会削弱UA的抗肿瘤特性，这进一步揭示了TGFβ在胶质母细胞瘤病理中的关键作用。支持这些实验室结果的是，UA在胶质母细胞瘤异种移植小鼠模型中也显示出对肿瘤生长的显著抑制作用。总体而言，我们的研究强调了熊果酸作为胶质母细胞瘤新治疗方法的前景，并阐明了其作用机制，主要是通过抑制TGFβ信号传导，从而抑制EMT和血管生成。
