Targeting Wee1 kinase to suppress proliferation and survival of cisplatin-resistant head and neck squamous cell carcinoma

Autor: Zejia Yang, Jipei Liao, Rena G. Lapidus, Xiaoxuan Fan, Ranee Mehra, Kevin J. Cullen, Hancai Dan
Rok vydání: 2022
Předmět:
Zdroj: Cancer Chemotherapy and Pharmacology. 89:469-478
ISSN: 1432-0843
0344-5704
Popis: We investigated the role of Wee1 kinase in cisplatin-resistant head and neck squamous cell carcinoma (HNSCC) in multiple cisplatin-resistant HNSCC cell lines and determined the efficacy of either Wee1 inhibitor, AZD1775 alone, or in combination with cisplatin, on cisplatin-resistant HNSCC inhibition.Phosphorylation and total protein levels of cells were assessed by Western blot analysis. Cell viability and apoptosis were examined by MTS assay and flow cytometry, respectively.Wee1 kinase protein expression levels in five cisplatin-resistant HNSCC cell types were higher than those in their parental cisplatin-sensitive partners. Importantly, Wee1 knockdown inhibited cell proliferation and re-sensitized cells to cisplatin treatment. Interestingly, previous studies have also shown that Wee1 inhibitor AZD1775 synergizes with cisplatin to suppress cell proliferation of cisplatin-sensitive HNSCC. We found that AZD1775 inhibited both cisplatin-sensitive and resistant HNSCC with similar ICWee1 inhibitor, AZD1775, and cisplatin coordinately suppressed proliferation and survival of HNSCC.
Databáze: OpenAIRE