ID 111278
Author
Tomida, Chisato Tokushima University
Aibara, Kana Tokushima University
Yamagishi, Naoko Tokushima University
Yano, Chiaki Tokushima University
Nagano, Hikaru Sagami Women’s University
Ohno, Ayako Tokushima University
Keywords
angiogenesis inhibitor
VEGF receptor tyrosine kinase inhibitor
regorafenib
colon cancer cells
malignant phenotype
Content Type
Journal Article
Description
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.
Journal Title
The Journal of Medical Investigation
ISSN
13496867
13431420
NCID
AA11166929
AA12022913
Publisher
Faculty of Medicine Tokushima University
Volume
62
Issue
3-4
Start Page
195
End Page
198
Sort Key
195
Published Date
2015-08
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Medical Sciences