Open Access

Osthole attenuates angiogenesis in an orthotopic mouse model of hepatocellular carcinoma via the downregulation of nuclear factor‑κB and vascular endothelial growth factor

  • Authors:
    • Fei Yao
    • Lurong Zhang
    • Guorong Jiang
    • Min Liu
    • Guoqiang Liang
    • Qin Yuan
  • View Affiliations

  • Published online on: July 25, 2018     https://doi.org/10.3892/ol.2018.9213
  • Pages: 4471-4479
  • Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Osthole has been demonstrated to have antitumor activity. Previous studies by our group indicated that osthole effectively inhibited tumor growth in hepatocellular carcinoma (HCC) through the induction of apoptosis and enhancement of antitumor immune responses in mice. The importance of angiogenesis in the proliferation, invasion and metastasis of tumor cells in HCC is well established. The present study aimed to investigate the effects of osthole on angiogenesis in an orthotopic mouse model of HCC. Orthotopic HCC in mice was established, and osthole at 61, 122 and 244 mg/kg was administered intraperitoneally once daily to the tumor‑bearing mice for 14 consecutive days. Immunohistochemistry was performed to analyze the microvessel density (MVD) of tissues, and the level of vascular endothelial growth factor (VEGF) was measured by ELISA. The protein levels of nuclear factor‑κB (NF‑κB) p65 and IκB‑α were also detected by western blotting. MVD was positively correlated with tumor weight in the orthotopic mouse model of HCC. Osthole administration significantly decreased MVD in tumor and adjacent tissues, and inhibited tumor growth. Furthermore, osthole downregulated the expression of VEGF and NF‑κB p65, and upregulated IκB‑α expression in tumor and adjacent tissues. To the best of our knowledge, the results of the present study demonstrated for the first time that osthole inhibits angiogenesis in an orthotopic mouse model of HCC, which may be one of the mechanisms underlying the anti‑HCC activity of osthole, which in turn may be mediated by the NF‑κB/VEGF signaling pathway. Therefore, osthole, a potential angiogenesis inhibitor and immune system enhancer, may be a promising lead compound for the treatment of HCC.
View Figures
View References

Related Articles

Journal Cover

October-2018
Volume 16 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Yao F, Zhang L, Jiang G, Liu M, Liang G and Yuan Q: Osthole attenuates angiogenesis in an orthotopic mouse model of hepatocellular carcinoma via the downregulation of nuclear factor‑κB and vascular endothelial growth factor. Oncol Lett 16: 4471-4479, 2018
APA
Yao, F., Zhang, L., Jiang, G., Liu, M., Liang, G., & Yuan, Q. (2018). Osthole attenuates angiogenesis in an orthotopic mouse model of hepatocellular carcinoma via the downregulation of nuclear factor‑κB and vascular endothelial growth factor. Oncology Letters, 16, 4471-4479. https://doi.org/10.3892/ol.2018.9213
MLA
Yao, F., Zhang, L., Jiang, G., Liu, M., Liang, G., Yuan, Q."Osthole attenuates angiogenesis in an orthotopic mouse model of hepatocellular carcinoma via the downregulation of nuclear factor‑κB and vascular endothelial growth factor". Oncology Letters 16.4 (2018): 4471-4479.
Chicago
Yao, F., Zhang, L., Jiang, G., Liu, M., Liang, G., Yuan, Q."Osthole attenuates angiogenesis in an orthotopic mouse model of hepatocellular carcinoma via the downregulation of nuclear factor‑κB and vascular endothelial growth factor". Oncology Letters 16, no. 4 (2018): 4471-4479. https://doi.org/10.3892/ol.2018.9213