Regorafenib induces adaptive resistance of colorectal cancer cells via inhibition of vascular endothelial growth factor receptor

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著者

    • Tomida Chisato
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Nagano Hikaru
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Yamagishi Naoko
    • Department of Anatomy and Cell Biology, School of Medicine, Wakayama Medical University
    • Uchida Takayuki
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Ohno Ayako
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Hirasaka Katsuya
    • Graduate school of Fisheries Science and Environmental Studies, Nagasaki University
    • Nikawa Takeshi
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Teshima-Kondo Shigetada
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School

抄録

<p>Recently, inhibition of tumor angiogenesis has become an important anti-cancer therapy. Tumor angiogenesis is regulated by multiple signaling pathways, including VEGF and VEGF receptor (VEGF-R), FGF and FGF receptor (FGF-R), and PDGF and PDGF receptor (PDGF-R) pathways. Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability. Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells. To identify the responsible receptor among the regorafenib-targeting proangiogenic receptors, we examined the effects of a potent selective inhibitor for VEGF-R, FGF-R or PDGF-R on apoptosis resistance and migration capability. We clarified that blockade of VEGF-R, but not FGF-R and PDGF-R, induced the malignant phenotypes. We confirmed that blocking of VEGF ligands derived from colorectal cancer cells also induced the phenotypes. These results suggest that regorafenib progressed the malignancy via prevention of autocrine and paracrine VEGF signaling in colorectal cancer cells. J. Med. Invest. 64: 262-265, August, 2017</p>

収録刊行物

  • The Journal of Medical Investigation

    The Journal of Medical Investigation 64(3.4), 262-265, 2017

    国立大学法人 徳島大学医学部

各種コード

  • NII論文ID(NAID)
    130006105177
  • NII書誌ID(NCID)
    AA11166929
  • 本文言語コード
    ENG
  • 資料種別
    journal article
  • ISSN
    1343-1420
  • データ提供元
    IR  J-STAGE 
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