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    Article

    Cordyceps militaris Fraction Inhibits Angiogenesis of Hepatocellular Carcinoma in vitro and in vivo

    Zhiwei Li2, Zhongyi Guo3, Jianhua Zhu4, Sixue Bi3, Yuanyuan Luo4, Rongmin Yu3,4, Weijuan Huang2, Liyan Song2★★ Corresponding author

    1. 1Department of Pharmacology, College of Pharmacy, China.
    2. 2Biotechnological Institute of Chinese Materia Medica, Jinan University, China.
    3. 3Department of Natural Product Chemistry, College of Pharmacy, Jinan University, Guangzhou, China.

    CORRESPONDENCE

    Liyan Song

    Biotechnological Institute of Chinese Materia Medica, Jinan University, China.

    tsly@jnu.edu.cn

    Received: 02-08-2019; Revised: 22-08-2019.

    Volume 16, Issue 67 · pp. 169–176 · PUBLISHED 11 February 2020 · DOI: 10.4103/pm.pm_347_19

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    Objectives: The objective of the study is to research the antiangiogenic activity of CMF in HCC cells and the underlying mechanism in vitro and in vivo. Materials and Methods: Transwell migration and invasion assays were used to measure the effects of CMF on migration and invasion of SMMC‑7721 cells and human umbilical vein endothelial cells (HUVECs). Tube formation and rat aortic ring assays were used to assess the antiangiogenic potential of CMF. The antiangiogenic mechanism was detected by immunofluorescence and western blot analysis. The nude mice xenografted with SMMC‑7721 cells were used to study the antiangiogenic activity of CMF and its underlying mechanism in vivo. Immunohistochemistry analysis was used to evaluate the effect of CMF on the expression of CD31, and western blot analysis was also performed to detect the expression of vascular endothelial growth factor (VEGF) and other related proteins in tumor tissues. Results: CMF inhibited the migration and invasion of SMMC‑7721 cells and HUVECs and suppressed VEGF‑induced tube formation of HUVECs and the formation of aortic ring capillaries of rats in a concentration‑dependent manner. CMF attenuated the phosphorylation of VEGF receptor 2 (VEGFR2), Akt, and ERK in SMMC‑7721 cells and HUVECs. CMF significantly inhibited tumor growth in nude mice xenografted with SMMC‑7721 cells. CMF reduced the expression level of CD31, western blot analysis indicated that CMF downregulated the expression of VEGFR2 and attenuated the phosphorylation of Akt and ERK in the tumor tissues, which was consistent with the results obtained from in vitro study. Conclusion: CMF can inhibit the angiogenesis of HCC and the mechanism is associated with suppression of the VEGF/VEGFR2 signaling pathway.

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      Li, Z., Guo, Z., Zhu, J., Bi, S., Luo, Y., Yu, R., Huang, W., & Song, L. (2020). Cordyceps militaris Fraction Inhibits Angiogenesis of Hepatocellular Carcinoma in vitro and in vivo. Pharmacognosy Magazine, 16(67), 169–176. https://doi.org/10.4103/pm.pm_347_19