Cx-4945 and sirna-mediated knockdown of ck2 improves cisplatin response in hpv(+) and hpv(-) hnscc cell lines

Janeen H Trembley, Bin Li, Betsy J Kren, Amy A Gravely, Emiro E Caicedo-Granados, Mark A Klein, Khalil Ahmed

Research output: Contribution to journalArticlepeer-review

Abstract

Head and neck squamous cell carcinoma (HNSCC) can be categorized into human papil-lomavirus (HPV) positive or negative disease. Elevated protein kinase CK2 level and activity have been historically observed in HNSCC cells. Previous studies on CK2 in HNSCC did not generally include consideration of HPV(+) and HPV(-) status. Here, we investigated the response of HPV(+) and HPV(-) HNSCC cells to CK2 targeting using CX-4945 or siRNA downregulation combined with cisplatin treatment. HNSCC cell lines were examined for CK2 expression levels and activity and response to CX-4945, with and without cisplatin. CK2 levels and NFκB p65-related activity were high in HPV(+) HNSCC cells relative to HPV(-) HNSCC cells. Treatment with CX-4945 decreased viability and cisplatin IC50 in all cell lines. Targeting of CK2 increased tumor suppressor protein levels for p21 and PDCD4 in most instances. Further study is needed to understand the role of CK2 in HPV(+) and HPV(-) HNSCC and to determine how incorporation of the CK2-targeted inhibitor CX-4945 could improve cisplatin response in HNSCC.

Original languageEnglish (US)
Article number571
JournalBiomedicines
Volume9
Issue number5
DOIs
StatePublished - May 18 2021

Bibliographical note

Funding Information:
Funding: This work was supported by Merit Review research funds I01 BX003282 and I01 BX005091 awarded by the United States Department of Veterans Affairs Biomedical Laboratory Research and Development Service (K.A.); Lion’s award (B.L.).

Funding Information:
Acknowledgments: K.A. holds the title of Senior Research Career Scientist awarded by the U.S. Department of Veterans Affairs. We thank Daniel P. Shaughnessy for technical assistance.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Cisplatin
  • CK2
  • Head and neck cancer
  • HNSCC
  • HPV
  • Human papillomavirus
  • NFκB
  • P21
  • PDCD4

PubMed: MeSH publication types

  • Journal Article

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