ID 111254
著者
Tomida, Chisato The University of Tokushima
Yamagishi, Naoko The University of Tokushima
Aibara, Kana The University of Tokushima
Yano, Chiaki The University of Tokushima
安倍, 知紀 The University of Tokushima KAKEN研究者をさがす
Ohno, Ayako The University of Tokushima
近藤, 茂忠 The University of Tokushima KAKEN研究者をさがす
キーワード
VEGF
VEGF-targeting drugs
colon cancer cells
malignant phenotype
資料タイプ
学術雑誌論文
抄録
VEGF-targeting anti-angiogenic drugs have enabled significant advances in cancer therapy. However, acquired resistance to VEGF-targeting drugs occurs, leading to disease progression. How tumors become the resistance remains fully uncertain. One of possible mechanisms for the resistance may be the direct effect of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGF-R). We investigated here the direct effect of chronic VEGF inhibition on phenotype changes in cancer cells. To chronically inhibit cancer cell-derived VEGF, human colon cancer HCT116 cells were chronically exposed (3 months) to anti-VEGF neutralizing monoclonal antibody (HCT/mAb cells, blockade of VEGF alone) or VEGF-R tyrosine kinase inhibitor foretinib (HCT/fore cells, blockade of all VEGF family). HCT/mAb cells redundantly increased VEGF family member (VEGF, PlGF, VEGF-B, VEGF-R1 and VEGF-R2) and induced a resistance to hypoxia-induced apoptosis. By contrast, HCT/fore cells did not show the redundant increase in VEGF family member, but significantly increased a VEGF-independent pro-angiogenic factor FGF-2. HCT/fore cells showed increased migration and invasion activities in addition to a resistance to hypoxia-induced apoptosis. The resistance to apoptosis was significantly suppressed by inhibition of hypoxia-inducible factor-1α in HCT/mAb cells, but not in HCT/fore cells. These findings suggest that chronic inhibition of VEGF/VEGF-R accelerates malignant phenotypes of colon cancer cells.
掲載誌名
The Journal of Medical Investigation
ISSN
13496867
13431420
cat書誌ID
AA11166929
AA12022913
出版者
Faculty of Medicine Tokushima University
62
1-2
開始ページ
75
終了ページ
79
並び順
75
発行日
2015-02
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
医学系