The impact of CDK9 on radiosensitivity, DNA damage repair and cell cycling of HNSCC cancer cells

  • Authors:
    • Katja Storch
    • Nils Cordes
  • View Affiliations

  • Published online on: November 13, 2015     https://doi.org/10.3892/ijo.2015.3246
  • Pages: 191-198
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

January-2016
Volume 48 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Storch K and Storch K: The impact of CDK9 on radiosensitivity, DNA damage repair and cell cycling of HNSCC cancer cells. Int J Oncol 48: 191-198, 2016
APA
Storch, K., & Storch, K. (2016). The impact of CDK9 on radiosensitivity, DNA damage repair and cell cycling of HNSCC cancer cells. International Journal of Oncology, 48, 191-198. https://doi.org/10.3892/ijo.2015.3246
MLA
Storch, K., Cordes, N."The impact of CDK9 on radiosensitivity, DNA damage repair and cell cycling of HNSCC cancer cells". International Journal of Oncology 48.1 (2016): 191-198.
Chicago
Storch, K., Cordes, N."The impact of CDK9 on radiosensitivity, DNA damage repair and cell cycling of HNSCC cancer cells". International Journal of Oncology 48, no. 1 (2016): 191-198. https://doi.org/10.3892/ijo.2015.3246