Developing of differentiation inducing therapy on oral cancer by targeting transcription factor Brachyury which regulates cancer stem cells

我们报道了T-box转录因子brachyury是肿瘤干细胞(CSCs)的潜在调节因子。具体地说，在ADCC中，CSCs的生长受短臂基因敲除的控制。由于CSCs对化疗和放疗具有耐药性，这一发现为针对CSCs的治疗提供了新的原则。在目前的研究中，我们在体外建立了短暂性基因敲除抑制化疗和放射抵抗的作用。将短发夹状RNA(ShRNA)导入ADCC CSC细胞系ACCS-M GFP中，将短发夹状RNA(ShRNA)导入ADCC CSC细胞系ACCS-M GFP中，将短发夹状RNA导入ADCC CSC细胞系ACCS-M GFP。短梗阻基因显著抑制细胞的迁移和侵袭，并抑制化疗耐药。此外，ACCS-M GFP的辐射抗性可被短臂基因敲除显著抑制。短臂基因敲除显著增加了ACCS-M GFP细胞对放化疗的敏感性。这项研究表明，短臂敲除降低了体内CSCs的侵袭性以及对化疗和辐射的抵抗力。

We reported that the T-box transcription factor Brachyury is a potential regulator of cancer stem cells (CSCs). Specifically, growth of CSCs was controlled by Brachyury knockdown in AdCC. Since CSCs are resistant to chemotherapy and radiotherapy, this finding provides a new principle for therapies targeting CSCs. In the present study, we established that Brachyury knockdown suppresses chemo- and radioresistance in vitro. Brachyury was knocked down by transfecting Brachyury short hairpin RNA (shRNA) into the AdCC CSC cell line, ACCS-M GFP. Brachyury knockdown significantly inhibited cell migration and invasion and suppressed chemoresistance. Furthermore, ACCS-M GFP radioresistance was significantly suppressed by Brachyury knockdown. Brachyury knockdown significantly sensitized ACCS-M GFP cells to chemoradiotherapy. This study demonstrates that Brachyury knockdown reduces invasiveness and chemo- and radioresistance of CSCs in vivo.