Skip to main content


  • Poster presentation
  • Open Access

P01.41. Melittin inhibits VEGF-A-induced tumor growth and angiogenesis through blocking VEGFR-2 and COX-2 in allograft tumor model and endothelial cells

  • 1,
  • 1,
  • 1,
  • 1,
  • 1 and
  • 1
BMC Complementary and Alternative MedicineThe official journal of the International Society for Complementary Medicine Research (ISCMR)201212 (Suppl 1) :P41

  • Published:


  • Lymphatic Endothelial Cell
  • Lewis Lung Cancer
  • Reduce Tumor Cell
  • Major Polypeptide
  • Inhibitor NS398


To evaluate the in vivo as well as in vitro anti-angiogenesis effects of melittin, a major polypeptide in bee venom, and to elucidate its molecular mechanisms with a special focus on VEGFR-2 mediated COX-2 and MAPK pathways in VEGF-A-induced Lewis lung cancer (VEGF-A-hm LLC) model and human lymphatic endothelial cells (VEGF-A-HLECs).


We investigated the functional specificity of melittin as an angiogenesis inhibitor using VEGF-A-induced in vitro models and an in vivo lung metastasis mouse model.


Injection of 0.5mg/kg and 5mg/kg of melittin suppressed tumor growth by 25.30% and 56.92%, respectively; these results are superior to those obtained for mice treated with the COX-2 inhibitor, NS398. Melittin reduced tumor cell proliferation (PCNA), microvessel density (MVD), expression of cyclooxygenase-2 (COX-2), VEGF-A, and VEGFR-2, but did not affect VEGFR-1, in VEGF-A-induced hm LLC tumors. Similarly, the COX-2 inhibitor NS398 significantly inhibited proliferation, MVD, COX-2, VEGF-A, and VEGFR-2 expression in the tumor section, supporting the role of COX-2 in melittin-induced inhibition of angiogenesis. Melittin significantly inhibited VEGF-A-induced proliferation and tube formation in the endothelial cells. Melittin inhibited phosphorylation of ERK 1/2, JNK and p38 MAPK in a dose-dependent manner in VEGF-A-HLECs. p38 inhibitor SB203580 abolished the down regulation of COX-2 and VEGF-A and anti-proliferative activity induced by melittin.


These results suggest that melittin suppresses VEGF-A-induced tumor growth and angiogenesis via VEGFR-2 mediated COX-2 and the MAPK-dependent pathway.

Authors’ Affiliations

Kyung Hee University, Seoul, Republic of Korea


© Huh et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.