Trembley Janeen H, Li Bin, Kren Betsy T, Gravely Amy A, Caicedo-Granados Emiro, Klein Mark A, Ahmed Khalil
Minneapolis VA Health Care System Research Service, Minneapolis, MN 55417, USA.
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Biomedicines. 2021 May 18;9(5):571. doi: 10.3390/biomedicines9050571.
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.
头颈部鳞状细胞癌（HNSCC）可分为人乳头瘤病毒（HPV）阳性或阴性疾病。历史上在HNSCC细胞中观察到蛋白激酶CK2水平和活性升高。以往关于HNSCC中CK2的研究通常未考虑HPV（+）和HPV（-）状态。在此，我们使用CX-4945或siRNA下调结合顺铂治疗，研究了HPV（+）和HPV（-）HNSCC细胞对CK2靶向的反应。检测了HNSCC细胞系的CK2表达水平、活性以及对CX-4945的反应，包括有无顺铂的情况。相对于HPV（-）HNSCC细胞，HPV（+）HNSCC细胞中的CK2水平和NFκB p65相关活性较高。用CX-4945处理降低了所有细胞系的活力和顺铂IC50。在大多数情况下，靶向CK2可提高p21和PDCD4等肿瘤抑制蛋白水平。需要进一步研究以了解CK2在HPV（+）和HPV（-）HNSCC中的作用，并确定加入CK2靶向抑制剂CX-4945如何改善HNSCC对顺铂的反应。
