title: Targeting fibroblast growth factor receptor 3 enhances radiosensitivity in human squamous cancer cells.
abstract: Conventional therapies including radiation therapy cannot cure squamous cell carcinoma (SCC), and new treatments are clearly required. Our recent studies have shown that SCC cell lines exhibiting radioresistance show significant upregulation of the fibroblast growth factor receptor 3 (FGFR3) gene. We hypothesized that inhibiting FGFR3 would suppress tumor cell radioresistance and provide a new treatment approach for human SCCs. In the present study, we found that RNA interference-mediated FGFR3 depletion in HSC-2 cells, a radioresistant cell line, induced radiosensitivity and inhibited tumor growth. Use of an FGFR3 inhibitor (PD173074) obtained similar results with suppression of the autophosphorylation extracellular signal-regulated kinase pathway in HSC-2 cells and lung cancer cell lines. Moreover, the antitumor growth effect of the combination of PD173074 and radiation in vivo was also greater than that with either drug alone or radiation alone. Our results provided novel information on which to base further mechanistic study of radiosensitization by inhibiting FGFR3 in human SCC cells and for developing strategies to improve outcomes with concurrent radiotherapy.
authors.affiliation: Department of Clinical Molecular Biology, Graduate School of Medicine, Chiba University, Chiba-shi, Chiba, Japan. uzawak@faculty.chiba-u.jp
authors.forename: K
authors.initials: K
authors.lastname: Uzawa
authors.forename: T
authors.initials: T
authors.lastname: Ishigami
authors.forename: K
authors.initials: K
authors.lastname: Fushimi
authors.forename: T
authors.initials: T
authors.lastname: Kawata
authors.forename: K
authors.initials: K
authors.lastname: Shinozuka
authors.forename: A
authors.initials: A
authors.lastname: Kasamatsu
authors.forename: Y
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: K
authors.initials: K
authors.lastname: Ogawara
authors.forename: M
authors.initials: M
authors.lastname: Shiiba
authors.forename: H
authors.initials: H
authors.lastname: Bukawa
authors.forename: H
authors.initials: H
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Tanzawa
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011743:Pyrimidines / Q000494:pharmacology; D011836:Radiation Tolerance; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics*; D017468:Receptors, Fibroblast Growth Factor / Q000037:antagonists & inhibitors
chemical_list: C115711:PD 173074; D011743:Pyrimidines; D017468:Receptors, Fibroblast Growth Factor; D051498:Receptor, Fibroblast Growth Factor, Type 3