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首页> 外文期刊>Translational Research in Oral Oncology >Resistance to dasatinib is associated with the activation of Akt in oral squamous cell carcinoma:
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Resistance to dasatinib is associated with the activation of Akt in oral squamous cell carcinoma:

机译：对达沙替尼的耐药性与口腔鳞状细胞癌中Akt的激活有关：

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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...
机译：目的：Src的过度表达和异常激活促进口腔鳞状细胞癌（OSCC）的发展，因此靶向Src相关激酶的疗法可能会改善患者的生存率。然而，靶向Src的药物dasatinib在癌症患者中的临床活性有限，值得进一步研究以更好地了解OSCC中对dasatinib耐药的潜在基础。方法：一组口腔癌细胞系对dasatinib的反应进行了评估，共3项-（4,5-二甲基噻唑-2-基）-2,5-二苯基四唑溴化物，DNA合成，细胞周期和凋亡分析。使用免疫印迹研究了药物反应的潜在机制。结果：所有细胞系均对达沙替尼敏感（IC50 <250 nM），但与CDKN2a / p14ARF突变无关。达沙替尼诱导的细胞周期停滞和凋亡，同时在所有测试的细胞系中均抑制Src，Akt和FAK活性。然而，达沙替尼未能抑制肿瘤的生长。

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