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ISSN Druckformat: 0731-8898
ISSN Online: 2162-6537
IF:
2.4
5-Year IF:
2.8
Immediacy Index:
0.5
Eigenfactor:
0.00049
JCI:
0.59
SJR:
0.429
SNIP:
0.507
CiteScore™::
3.9
H-Index:
49
Indexed in
Vernolide-A Inhibits Radiation-Induced Hypoxia-Mediated Tumor Angiogenesis by Regulating HIF-1α, MMP-2, MMP-9, and VEGF
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ABSTRAKT
We investigated the effect of vernolide-A on the inhibition of radiation-induced tumor angiogenesis in C57BL/6 mice. Vernolide-A administration significantly reduced the tumor volume of radiation-exposed mice. Serum vascular endothelial growth factor (VEGF) levels were drastically elevated during tumor progression and irradiation and were significantly reduced by treatment with vernolide-A. Immunohistochemical analysis also revealed reduced vascular density after treatment with vernolide-A, and 3H-thymidine incorporation assay and soft agar assay showed that vernolide-A could inhibit the proliferation of B16F-10 melanoma cells in vitro along with radiation. Vernolide-A also caused a significant inhibition in the invasion of irradiated B16F-10 melanoma cells across the collagen matrix, and inhibited the radiation-induced gene expression of hypoxia-inducible transcription factor-1α (HIF-1α) and VEGF in B16F-10 cells and VEGF receptor (Flk-1) expression in human umbilical vein endothelial cells. Gelatin zymographic analysis showed that vernolide-A could also inhibit the radiation-induced activation of matrix metalloproteinases (MMPs). Our results indicate that vernolide-A inhibits radiation-induced tumor angiogenesis by regulating HIF-1α, MMP-2, MMP-9, and VEGF.
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