The malignant progression effects of regorafenib in human colon cancer cells

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Author(s)

    • Tomida Chisato
    • Department of Physiological Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Teshima-Kondo Shigetada
    • Department of Physiological Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Aibara Kana
    • Department of Physiological Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Yamagishi Naoko
    • Department of Physiological Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Yano Chiaki
    • Department of Physiological Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Abe Tomoki
    • Department of Physiological Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Ohno Ayako
    • Department of Physiological Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School
    • Hirasaka Katsuya
    • Graduate school of Fisheries Science and Environmental Studies, Nagasaki University
    • Nikawa Takeshi
    • Department of Physiological Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School

Abstract

A number of anti-angiogenic drugs targeting vascular endothelial growth factor receptors (VEGF-R) have developed and enabled significant advances in cancer therapy including colorectal cancer. However, acquired resistance to the drugs occurs, leading to disease progression, such as invasion and metastasis. How tumors become the resistance and promote their malignancy remains fully uncertain. One of possible mechanisms for the resistance and the progression may be the direct effect of VEGF-R inhibitors on tumor cells expressing VEGF-R. We investigated here the direct effect of a VEGF-R-targeting agent, regorafenib, which is the first small molecule inhibitor of VEGF-Rs for the treatment of patients with colorectal cancer, on phenotype changes in colon cancer HCT116 cells. Treatment of cells with regorafenib for only 2 days activated cell migration and invasion, while vehicle-treated control cells showed less activity. Intriguingly, chronic exposure to regorafenib for 90 days dramatically increased migration and invasion activities and induced a resistance to hypoxia-induced apoptosis. These results suggest that loss of VEGF signaling in cancer cells may induce the acquired resistance to VEGF/VEGF-R targeting therapy by gaining two major malignant phenotypes, apoptosis resistance and activation of migration/invasion. J. Med. Invest. 62: 195-198, August, 2015

Journal

  • The Journal of Medical Investigation

    The Journal of Medical Investigation 62(3.4), 195-198, 2015

    Faculty of Medicine Tokushima University

Codes

  • NII Article ID (NAID)
    130005099146
  • NII NACSIS-CAT ID (NCID)
    AA11166929
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    1343-1420
  • Data Source
    IR  J-STAGE 
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