Regorafenib induces adaptive resistance of colorectal cancer cells via inhibition of vascular endothelial growth factor receptor
| Autor: | Shigetada Teshima-Kondo, Takeshi Nikawa, Naoko Yamagishi, Ayako Ohno, Hikaru Nagano, Katsuya Hirasaka, Chisato Tomida, Takayuki Uchida |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pyridines Angiogenesis Inhibitors Apoptosis Fibroblast growth factor General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound Paracrine signalling 0302 clinical medicine Cell Movement Regorafenib Humans VEGF-R Autocrine signalling tumor cell aggressiveness biology Phenylurea Compounds General Medicine Protein-Tyrosine Kinases HCT116 Cells Angiogenesis inhibitor 030104 developmental biology angiogenesis inhibitor Receptors Vascular Endothelial Growth Factor chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research regorafenib Signal transduction Colorectal Neoplasms Platelet-derived growth factor receptor |
| Zdroj: | The journal of medical investigation : JMI. 64(3.4) |
| ISSN: | 1349-6867 |
| Popis: | Recently, inhibition of tumor angiogenesis has become an important anti-cancer therapy. Tumor angiogenesis is regulated by multiple signaling pathways, including VEGF and VEGF receptor (VEGF-R), FGF and FGF receptor (FGF-R), and PDGF and PDGF receptor (PDGF-R) pathways. Thus, the antiangiogenic agents, such as regorafenib, simultaneously target those receptors on vascular endothelial cells. In addition to endothelial cells, cancer cells express the three receptors, suggesting that the antiangiogenic inhibitors affect tumor cells. In fact, we previously demonstrated that regorafenib directly acted on human colorectal cancer cells and accelerated their apoptosis resistance and migration capability. Thus, we here elucidated how regorafenib induced the malignant phenotypes in colorectal cancer cells. To identify the responsible receptor among the regorafenib-targeting proangiogenic receptors, we examined the effects of a potent selective inhibitor for VEGF-R, FGF-R or PDGF-R on apoptosis resistance and migration capability. We clarified that blockade of VEGF-R, but not FGF-R and PDGF-R, induced the malignant phenotypes. We confirmed that blocking of VEGF ligands derived from colorectal cancer cells also induced the phenotypes. These results suggest that regorafenib progressed the malignancy via prevention of autocrine and paracrine VEGF signaling in colorectal cancer cells. J. Med. Invest. 64: 262-265, August, 2017. |
| Databáze: | OpenAIRE |
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