CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines
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 HP...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-05-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/9/5/571 |
| _version_ | 1827692240383770624 |
|---|---|
| author | Janeen H. Trembley Bin Li Betsy T. Kren Amy A. Gravely Emiro Caicedo-Granados Mark A. Klein Khalil Ahmed |
| author_facet | Janeen H. Trembley Bin Li Betsy T. Kren Amy A. Gravely Emiro Caicedo-Granados Mark A. Klein Khalil Ahmed |
| author_sort | Janeen H. Trembley |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:17:34Z |
| format | Article |
| id | doaj.art-e916da35ab43400cbc1b96e5ef289ab9 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T11:17:34Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-e916da35ab43400cbc1b96e5ef289ab92023-11-21T20:18:17ZengMDPI AGBiomedicines2227-90592021-05-019557110.3390/biomedicines9050571CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell LinesJaneen H. Trembley0Bin Li1Betsy T. Kren2Amy A. Gravely3Emiro Caicedo-Granados4Mark A. Klein5Khalil Ahmed6Minneapolis VA Health Care System Research Service, Minneapolis, MN 55417, USAMinneapolis VA Health Care System Otolaryngology Section, Minneapolis, MN 55417, USAMinneapolis VA Health Care System Research Service, Minneapolis, MN 55417, USAMinneapolis VA Health Care System Research Service, Minneapolis, MN 55417, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAMasonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USAMinneapolis VA Health Care System Research Service, Minneapolis, MN 55417, USAHead 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.https://www.mdpi.com/2227-9059/9/5/571head and neck cancerHNSCChuman papillomavirusHPVCK2NFκB |
| spellingShingle | Janeen H. Trembley Bin Li Betsy T. Kren Amy A. Gravely Emiro Caicedo-Granados Mark A. Klein Khalil Ahmed CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines Biomedicines head and neck cancer HNSCC human papillomavirus HPV CK2 NFκB |
| title | CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines |
| title_full | CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines |
| title_fullStr | CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines |
| title_full_unstemmed | CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines |
| title_short | CX-4945 and siRNA-Mediated Knockdown of CK2 Improves Cisplatin Response in HPV(+) and HPV(−) HNSCC Cell Lines |
| title_sort | cx 4945 and sirna mediated knockdown of ck2 improves cisplatin response in hpv and hpv hnscc cell lines |
| topic | head and neck cancer HNSCC human papillomavirus HPV CK2 NFκB |
| url | https://www.mdpi.com/2227-9059/9/5/571 |
| work_keys_str_mv | AT janeenhtrembley cx4945andsirnamediatedknockdownofck2improvescisplatinresponseinhpvandhpvhnscccelllines AT binli cx4945andsirnamediatedknockdownofck2improvescisplatinresponseinhpvandhpvhnscccelllines AT betsytkren cx4945andsirnamediatedknockdownofck2improvescisplatinresponseinhpvandhpvhnscccelllines AT amyagravely cx4945andsirnamediatedknockdownofck2improvescisplatinresponseinhpvandhpvhnscccelllines AT emirocaicedogranados cx4945andsirnamediatedknockdownofck2improvescisplatinresponseinhpvandhpvhnscccelllines AT markaklein cx4945andsirnamediatedknockdownofck2improvescisplatinresponseinhpvandhpvhnscccelllines AT khalilahmed cx4945andsirnamediatedknockdownofck2improvescisplatinresponseinhpvandhpvhnscccelllines |