The malignant progression effects of regorafenib in human colon cancer cells
| Autor: | Shigetada Teshima-Kondo, Chiaki Yano, Chisato Tomida, Katsuya Hirasaka, Ayako Ohno, Naoko Yamagishi, Tomoki Abe, Takeshi Nikawa, Hikaru Nagano, Kana Aibara |
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| Rok vydání: | 2015 |
| Předmět: |
Pyridines
Colorectal cancer VEGF receptor tyrosine kinase inhibitor Apoptosis Drug resistance Biology General Biochemistry Genetics and Molecular Biology Metastasis chemistry.chemical_compound Cell Movement Regorafenib medicine Humans Neoplasm Invasiveness malignant phenotype Phenylurea Compounds Cell migration General Medicine HCT116 Cells medicine.disease Angiogenesis inhibitor Vascular endothelial growth factor Receptors Vascular Endothelial Growth Factor angiogenesis inhibitor chemistry Drug Resistance Neoplasm Colonic Neoplasms Cancer cell Immunology Disease Progression Cancer research regorafenib colon cancer cells |
| Zdroj: | The Journal of Medical Investigation. 62:195-198 |
| ISSN: | 1349-6867 1343-1420 |
| DOI: | 10.2152/jmi.62.195 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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