Hughes Veronica S, Siemann Dietmar W
Department of Radiation Oncology, University of Florida, Gainesville, FL.
Tumor Microenviron. 2018;1(1):30-36. doi: 10.4103/tme.tme_19_17. Epub 2018 Jan 30.
The src inhibitor Dasatinib has been widely studied as an anti-metastatic agent. The aims of this study were to examine the effect of Src inhibition on the metastatic potential of the 4T1 murine mammary carcinoma.
Src is a non-receptor tyrosine kinase well-known to contribute to the metastatic potential of tumour cells. It does so through alteration of signalling pathways important to metastasis. Elevated levels of Src are common in many cancer types, and have been correlated with tumour progression and poor patient prognosis.
This study examined whether disruption of the Src signalling pathway could inhibit metastases formation.
The Src inhibitor Dasatinib was evaluated and using the highly metastatic 4T1 murine mammary adenocarcinoma cell line.
assays included growth curve, western blot, migration, and invasion assays. assays included intradermal and tail vein injection models.
data were analysed using one-way ANOVA with Dunnett's multiple comparisons in GraphPad Prism 6.0. data were analysed using GraphPad Prism 6.0, using the Wilcoxon matched pairs test.
Dasatinib is effective at inhibiting phosphorylation of Src, migration and invasion in the 4T1 cell line, as well as angiogenesis . treatment with Dasatinib impaired the metastatic ability of tumour cells as assessed by a tail vein injection model. However, both the syngeneic BALB/c and the athymic nu/nu mice receiving oral doses of the drug developed significantly higher numbers of 4T1 lung metastases. This effect was not seen in a different breast carcinoma cell line, the MDA-MB-231-4175-LM2, nor was this effect seen in the murine fibrosarcoma KHT cell line.
The 4T1 cell line is not an appropriate model to study Src inhibition.
Src抑制剂达沙替尼作为一种抗转移药物已得到广泛研究。本研究的目的是检验Src抑制对4T1小鼠乳腺癌转移潜能的影响。
Src是一种非受体酪氨酸激酶，众所周知它有助于肿瘤细胞的转移潜能。它通过改变对转移重要的信号通路来实现这一点。Src水平升高在许多癌症类型中很常见，并且与肿瘤进展和患者预后不良相关。
本研究检验了Src信号通路的破坏是否能抑制转移形成。
使用高转移性的4T1小鼠乳腺腺癌细胞系评估Src抑制剂达沙替尼。
实验包括生长曲线、蛋白质免疫印迹、迁移和侵袭实验。实验包括皮内和尾静脉注射模型。
数据在GraphPad Prism 6.0中使用单因素方差分析和Dunnett多重比较进行分析。数据在GraphPad Prism 6.0中使用Wilcoxon配对检验进行分析。
达沙替尼可有效抑制4T1细胞系中Src的磷酸化、迁移和侵袭以及血管生成。通过尾静脉注射模型评估，达沙替尼治疗损害了肿瘤细胞的转移能力。然而，接受口服该药物的同基因BALB/c小鼠和无胸腺裸鼠均出现了显著更多的4T1肺转移灶。在另一种乳腺癌细胞系MDA-MB-231-4175-LM2中未观察到这种效应，在小鼠纤维肉瘤KHT细胞系中也未观察到这种效应。
4T1细胞系不是研究Src抑制的合适模型。
