Resistance to dasatinib is associated with the activation of Akt in oral squamous cell carcinoma:

Translational Research in Oral Oncology

Pei SanYee¹ 

关键词: Oral squamous cell carcinoma;    targeted therapy;    cell signalling;    Src kinase;    xenografts;   

DOI  :  10.1177/2057178X17702920

学科分类：医学（综合）

来源: Sage Journals

【 摘 要 】

Objectives:Overexpression and aberrant activation of Src promote the development of oral squamous cell carcinoma (OSCC), thus therapies targeting Src-related kinases may afford an improvement in patient survival. However, limited clinical activity of the Src-targeted drug, dasatinib, in cancer patients warrants further investigation to better understand the underlying basis of resistance to dasatinib in OSCC.Methods:Response to dasatinib was evaluated in a panel of oral cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DNA synthesis, cell cycle and apoptosis analysis. The underlying mechanism of drug response was investigated using immunoblotting. Xenograft models were used to test efficacy.Results:All cell lines were sensitive to dasatinib (IC50 < 250 nM), but this was not associated with CDKN2a/p14ARF mutations. Dasatinib-induced cell cycle arrest and apoptosis, while inhibiting Src, Akt and FAK activity in all lines tested. However, dasatinib failed to inhibit tumour gr...

【 授权许可】

CC BY