1. Department of Neurosurgery, First Affiliated Hospital of Anhui Medical University, Hefei City, Anhui Province, China 230032.
2. Department of Neurosurgery, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu City, Sichuan Province, 611731, China.
Raddeanin A (RA), an oleanane-type triterpenoid saponin derived from Anemone raddeana Regel, has been found to suppress the viability and metastasis of several cancers, including GBM, through various signaling pathways. However, the mechanisms underlying the anti-GBM properties of RA have not been fully elucidated. Epithelial to mesenchymal transition (EMT) and angiogenesis are important for the genesis and progression of GBM. These two crucial processes can be regulated by multiple molecular, including β-catenin, which has been demonstrated to act as a pro-tumorigenic molecular. In this study, we aimed to determine whether RA could suppress EMT and angiogenesis by inhibiting the action of β-catenin in GBM. We found that RA inhibited the proliferation, invasion and migratory properties of GBM cells. RA was also found to have downregulated the expressions of β-catenin and EMT-related biomarkers (N-cadherin, vimentin, and snail). In addition, the overexpression of β-catenin reversed the therapeutic effects of RA exerted on the EMT of GBM cells. RA restricted angiogenesis, as shown by the tube formation assay and CAM assay, while it downregulated VEGF levels in HUVECs. Moreover, massive β-catenin could reverse the suppression of angiogenesis induced by RA. Finally, we demonstrated that RA inhibited tumor growth and prolonged survival time in an intracranial U87 xenograft mouse model. Similar to the results in vitro, RA downregulated the expression of β-catenin, EMT makers and VEGF, and decreased vessel density in vivo. In summary, our results demonstrated that RA repressed GBM via downregulating β-catenin-mediated EMT and angiogenesis both in vitro and in vivo.
Keywords: Raddeanin A, EMT, angiogenesis, β-catenin, glioblastoma.