title: The impact of CDK9 on radiosensitivity, DNA damage repair and cell cycling of HNSCC cancer cells.
abstract: Cyclin-dependent kinase 9 (CDK9), mainly involved in regulation of transcription, has recently been shown to impact on cell cycling and DNA repair. Despite the fact that CDK9 has been proposed as potential cancer target, it remains largely elusive whether CDK9 targeting alters tumor cell radiosensitivity. Five human head and neck squamous cell carcinoma (HNSCC) cell lines (SAS, FaDu, HSC4, Cal33, UTSCC5) as well as SAS cells stably transfected with CDK9-EGFP-N1 plasmid or empty vector controls were used. Upon either CDK9 small interfering RNA knockdown or treatment with a pan-CDK inhibitor (ZK304709), colony formation, DNA double strand breaks (DSBs), apoptosis, cell cycling, and expression and phosphorylation of major cell cycle and DNA damage repair proteins were examined. While CDK9 overexpression mediated radioprotection, CDK9 depletion clearly enhanced the radiosensitivity of HNSCC cells without an induction of apoptosis. While the cell cycle and cell cycle proteins were significantly modulated by CDK9 depletion, no further alterations in these parameters were observed after combined CDK9 knockdown with irradiation. ZK304709 showed concentration-dependent cytotoxicity but failed to radiosensitize HNSCC cells. Our findings suggest a potential role of CDK9 in the radiation response of HNSCC cells. Additional studies are warranted to clarify the usefulness to target CDK9 in the clinic.
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, D-01307 Dresden, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Storch
authors.affiliation: OncoRay - National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, D-01307 Dresden, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Cordes
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002470:Cell Survival / Q000528:radiation effects; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D011836:Radiation Tolerance / Q000187:drug effects / Q000235:genetics; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D018797:Cell Cycle Proteins; D011838:Radiation-Sensitizing Agents; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9