Department of Cardiovascular Surgery, Zhongnan Hospital, Wuhan University, Wuhan, China , tanghaoth@126.com
Abstract: (14 Views)
Background: The blockade of both VEGF / VEGFR and angiopoietin/TEK receptor tyrosine kinase (Tie-2) pathways can be considered an attractive approach to inhibition of angiogenesis in glioblastomas. Paeonol (Pae), a natural compound, has been identified to possess evidence of antitumor activity. Materials and Methods: In this study, the impact of Pae combined with radiotherapy on the glioblastoma angiogenesis pathways was investigated in vitro. For this purpose, effects of various doses of Pae alone or in combination of 2 Gy radiation was assessed using various endpoints such as gene expression, ᵧH2AX and apoptosis in glioblastoma cells. Results: Results indicated that Pae could induce the down-regulation of VEGF at the protein level and inhibit the mRNA and protein level of VEGFR1/2 in EA.hy926 cells. Pae and radiation co-treatment inhibited the protein levels of ANG1 and ANG2 in U251 cells and of Tie-2 in EA.hy926 cells. Notably, the combination therapy disrupted endothelial tube formation more effectively than Pae or radiation alone, reducing tubule length by 65% (p<0.001). However, we found that Pae had reduced the phosphorylation of Erk pathway in these cells. Pae enhanced radiation-induced DNA damage, as evidenced by increased γ-H2AX foci formation (p<0.01). The results further elucidate the multifaceted effects of Pae on tumor cell proliferation and angiogenesis in glioblastoma. Conclusion: Obtained results might imply that Pae might inhibit glioblastoma angiogenesis by the VEGF/VEGFR and ANG/Tie-2 pathways, with the Erk pathway potentially serving as a key mechanism. Our findings propose that Pae acts as a radiosensitizer while concurrently suppressing angiogenic signaling.
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