The malignant progression effects of regorafenib in human colon cancer cells

Chisato Tomida; Kana Aibara; Naoko Yamagishi; Chiaki Yano; Hikaru Nagano; Tomoki Abe; Ayako Ohno; Katsuya Hirasaka; Takeshi Nikawa; Shigetada Teshima-Kondo

doi:10.2152/jmi.62.195

Originals

The malignant progression effects of regorafenib in human colon cancer cells

Chisato Tomida, Kana Aibara, Naoko Yamagishi, Chiaki Yano, Hikaru Nagano, Tomoki Abe, Ayako Ohno, Katsuya Hirasaka, Takeshi Nikawa, Shigetada Teshima-Kondo

Author information

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

Keywords: angiogenesis inhibitor, VEGF receptor tyrosine kinase inhibitor, regorafenib, colon cancer cells, malignant phenotype

JOURNAL FREE ACCESS

2015 Volume 62 Issue 3.4 Pages 195-198

DOI https://doi.org/10.2152/jmi.62.195

Details

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

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