DDA suppresses angiogenesis and tumor growth of colorectal cancer in vivo through decreasing VEGFR2 signaling

Shiu Wen Huang, Jin Cherng Lien, Sheng Chu Kuo, Tur Fu Huang

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

As angiogenesis is required for tumor growth and metastasis, suppressing angiogenesis is a promising strategy in limiting tumor progression. Vascular endothelial growth factor (VEGF)-A, a critical pro-angiogenic factor, has thus become an attractive target for therapeutic interventions in cancer. In this study, we explored the underlying mechanisms of a novel anthraquinone derivative DDA in suppressing angiogenesis. DDA inhibited VEGF-A-induced proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs). DDA also reduced VEGF-A-induced microvessel sprouting from aortic rings ex vivo and suppressed neovascularization in vivo. VEGF-A-induced VEGFR1, VEGFR2, FAK, Akt, ERK1/2 or STAT3 phosphorylation was reduced in the presence of DDA. In addition, NRP-1 siRNA reduced VEGF-A's enhancing effects in VEGFR2, FAK and Akt phosphorylation and cell proliferation in HUVECs. DDA disrupted VEGF-A-induced complex formation between NRP-1 and VEGFR2. Furthermore, systemic administration of DDA was shown to suppress tumor angiogenesis and growth in in vivo mouse xenograft models. Taken together, we demonstrated in this study that DDA exhibits anti-angiogenic properties through suppressing VEGF-A signaling. These observations also suggest that DDA might be a potential drug candidate for developing anti-angiogenic agent in the field of cancer and angiogenesis-related diseases.

Original languageEnglish
Pages (from-to)63124-63137
Number of pages14
JournalOncotarget
Volume7
Issue number39
DOIs
Publication statusPublished - Jan 1 2016
Externally publishedYes

Fingerprint

Colorectal Neoplasms
Vascular Endothelial Growth Factor A
Growth
Neoplasms
Human Umbilical Vein Endothelial Cells
Phosphorylation
Anthraquinones
bis(p-chlorophenyl)acetic acid
Angiogenesis Inducing Agents
Microvessels
Heterografts
Small Interfering RNA
Cell Proliferation
Neoplasm Metastasis
Pharmaceutical Preparations

Keywords

  • Angiogenesis
  • Anthraquinone
  • Endothelial cells
  • VEGFR

ASJC Scopus subject areas

  • Oncology

Cite this

DDA suppresses angiogenesis and tumor growth of colorectal cancer in vivo through decreasing VEGFR2 signaling. / Huang, Shiu Wen; Lien, Jin Cherng; Kuo, Sheng Chu; Huang, Tur Fu.

In: Oncotarget, Vol. 7, No. 39, 01.01.2016, p. 63124-63137.

Research output: Contribution to journalArticle

Huang, Shiu Wen ; Lien, Jin Cherng ; Kuo, Sheng Chu ; Huang, Tur Fu. / DDA suppresses angiogenesis and tumor growth of colorectal cancer in vivo through decreasing VEGFR2 signaling. In: Oncotarget. 2016 ; Vol. 7, No. 39. pp. 63124-63137.
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