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Article

CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines

by 1,2,3,*,†, 4,5,†,§, 1,3, 1, 3,4,5,‡, 3,6,7,‡ and 1,2,3,5,‡
1
Minneapolis VA Health Care System Research Service, Minneapolis, MN 55417, USA
2
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
3
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
4
Minneapolis VA Health Care System Otolaryngology Section, Minneapolis, MN 55417, USA
5
Department of Otolaryngology, University of Minnesota, Minneapolis, MN 55455, USA
6
Minneapolis VA Health Care System Hematology and Oncology Section, Minneapolis, MN 55455, USA
7
Department of Medicine, University of Minnesota, One Veterans Drive, Minneapolis, MN 55417, USA
*
Author to whom correspondence should be addressed.
Equal contributions by authors.
Co-senior authors.
§
Current address: Kaiser Permanente Roseville Medical Center, Department of Head and Neck Surgery, 1600 Eureka Rd, Medical Office Building D, Roseville, CA 95661, USA.
Academic Editor: Veronique Baud
Received: 13 April 2021 / Revised: 7 May 2021 / Accepted: 13 May 2021 / Published: 18 May 2021
(This article belongs to the Special Issue CK2 Regulation of Cell Death and Targeting in Cancer Treatment)
Head and neck squamous cell carcinoma (HNSCC) can be categorized into human papillomavirus (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. View Full-Text
Keywords: head and neck cancer; HNSCC; human papillomavirus; HPV; CK2; NFκB; cisplatin; PDCD4; p21 head and neck cancer; HNSCC; human papillomavirus; HPV; CK2; NFκB; cisplatin; PDCD4; p21
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MDPI and ACS Style

Trembley, J.H.; Li, B.; Kren, B.T.; Gravely, A.A.; Caicedo-Granados, E.; Klein, M.A.; Ahmed, K. CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines. Biomedicines 2021, 9, 571. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050571

AMA Style

Trembley JH, Li B, Kren BT, Gravely AA, Caicedo-Granados E, Klein MA, Ahmed K. CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines. Biomedicines. 2021; 9(5):571. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050571

Chicago/Turabian Style

Trembley, Janeen H., Bin Li, Betsy T. Kren, Amy A. Gravely, Emiro Caicedo-Granados, Mark A. Klein, and Khalil Ahmed. 2021. "CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines" Biomedicines 9, no. 5: 571. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9050571

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