title: Fenofibrate increases radiosensitivity in head and neck squamous cell carcinoma via inducing G2/M arrest and apoptosis.
abstract: Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/ or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.
authors.affiliation: Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China E-mail : sunxinchen2012@163.com.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Yang-Yang
authors.initials: YY
authors.lastname: Ge
authors.forename: Hong-Cheng
authors.initials: HC
authors.lastname: Zhu
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.forename: Liang-Liang
authors.initials: LL
authors.lastname: Zhan
authors.forename: Qin
authors.initials: Q
authors.lastname: Qin
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Chen
authors.forename: Zhe-Ming
authors.initials: ZM
authors.lastname: Liu
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Ma
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Cheng
authors.forename: Xin-Chen
authors.initials: XC
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D016203:CDC2 Protein Kinase; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D056744:Cyclin B1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D000077195:Squamous Cell Carcinoma of Head and Neck; D023041:Xenograft Model Antitumor Assays
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; D011838:Radiation-Sensitizing Agents; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D053148:Caspase 3; D011345:Fenofibrate