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к Opioids inhibit tumor angiogenesis by suppressing VEGF signaling

Kohei Yamamizu1, Sadayoshi Furuta, Yusuke Hamada

  • 11] Laboratory of Stem Cell Differentiation, Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan [2] Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan [3] Laboratory of Genetics, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA [4].

Scientific Reports
|November 15, 2013
PubMed

Insights

Kappa opioid receptor (KOR) agonists inhibit tumor angiogenesis, offering a novel cancer therapy strategy. These findings highlight KOR agonists

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Opioids are crucial for managing cancer pain.
  • Tumor angiogenesis is vital for cancer growth and metastasis.

Purpose of the Study:

  • To investigate the role of opioid receptors in tumor angiogenesis.
  • To explore kappa opioid receptor (KOR) agonists as potential anti-angiogenic agents in cancer therapy.

Main Methods:

  • In vitro studies using human umbilical vein endothelial cells (HUVECs) treated with KOR agonists (U50,488H, TRK820) and other opioid receptor agonists (DAMGO, SNC80).
  • Assessment of VEGFR2 expression, HUVEC migration, and tube formation.
  • In vivo studies using KOR knockout mice and wild-type mice with grafted Lewis lung carcinoma (LLC) or B16 melanoma.
  • Evaluation of tumor growth and angiogenesis following TRK820 treatment.

Main Results:

  • KOR agonists significantly inhibited HUVEC migration and tube formation by suppressing VEGFR2 expression.
  • μ and δ opioid receptor agonists did not affect angiogenesis in HUVECs.
  • Tumors in KOR knockout mice exhibited increased proliferation and enhanced angiogenesis compared to wild-type mice.
  • TRK820 treatment significantly inhibited tumor growth and suppressed tumor angiogenesis.

Conclusions:

  • Kappa opioid receptor (KOR) agonists demonstrate anti-angiogenic properties.
  • KOR agonists represent a potential novel therapeutic strategy for cancer by targeting tumor angiogenesis.

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