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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Verstraete, Maud Debucquoy, Annelies Gonnissen, Annelies Dok, Ruveyda Isebaert, Sofie Devos, Ellen McBride, William Haustermans, Karin |
| Abstract | Background We examined the anti-tumor effect and radiosensitizing potential of a small molecule inhibitor of fibroblast growth factor receptor (FGFR) in colorectal cancer (CRC) in vitro and in vivo. Methods Effects of in vitro drug treatment on cell survival, proliferation, FGFR signaling, cell cycle distribution, apoptosis and radiosensitivity were assessed using various CRC cell lines with FGFR wild type (Caco2 and HCA7) and FGFR2 amplification (HCT116, NCI-H716). In vivo tumor responses to FGFR inhibition with and without radiation therapy were evaluated by growth delay assays in two colorectal xenograft mouse models (NMRI nu/nu mice injected with NCI-H716 or CaCo2 cells). Mechanistic studies were conducted using Western blot analysis, immunohistochemistry and qPCR. Results In the tested cell lines, the FGFR inhibitor (JNJ-42756493) was effective in vitro and in vivo in CRC tumors with highest expression of FGFR2 (NCI-H716). In vitro, cell proliferation in this line was decreased, associated with increased apoptotic death and decreased cell survival. In vivo, growth of NCI-H716 tumors was delayed by 5 days by drug treatment alone, although when drug delivery was stopped the relative tumor volume increased compared to control. The FGFR inhibitor did not radiosensitize NCI-H716 tumors either in vitro or in vivo. Conclusions Among tested CRC cell lines, the growth inhibitory activity of this FGFR inhibitor was evident in cell lines with high constitutive FGFR2 expression, suggesting that FGFR addiction may provide a window for therapeutic intervention, though caution is advised. Preclinical study with NCI-H716 and Caco2 tumor demonstrated that continued presence of drug could be essential for tumor growth control, especially in cells with aberrant FGFR expression. In the tested set-up, the inhibitor showed no radiosensitizing effect. |
| Related Links | https://bmccancer.biomedcentral.com/counter/pdf/10.1186/s12885-015-2000-8.pdf |
| Ending Page | 11 |
| Page Count | 11 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 14712407 |
| DOI | 10.1186/s12885-015-2000-8 |
| Journal | BMC Cancer |
| Issue Number | 1 |
| Volume Number | 15 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2015-12-16 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology Surgical Oncology Health Promotion and Disease Prevention Biomedicine Medicine Public Health Colorectal cancer Cancer therapy FGFR In vitro In vivo Radiotherapy Medicine/Public Health |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cancer Research Oncology Genetics |
| Journal Impact Factor | 3.4/2023 |
| 5-Year Journal Impact Factor | 3.8/2023 |
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