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为提高茶氨酸的活性,开发新型抗肿瘤药物,合成了新的茶氨酸衍生物茶双溴香酰胺(DTBr C),比较茶氨酸和茶双溴香酰胺对高转移的人乳腺癌MDA-MB-231细胞生长的抑制作用与其分子机制。采用MTT方法检测不同浓度的DTBr C对MDA-MB-231细胞生长的影响,应用蛋白质印迹法检测解析MDA-MB-231细胞中与凋亡和生长密切相关蛋白的表达和药物可能的作用靶点。结果表明,DTBr C抑制MDA-MB-231细胞生长的活性超过其母体化合物茶氨酸多倍;DTBr C显著减少抗凋亡蛋白Bcl-2水平,大大提高促凋亡蛋白Bax表达,从而减少Bcl-2/Bax比率;此外,DTBr C明显抑制血管内皮生长因子受体VEGFR2和蛋白激酶Akt的表达及磷酸化,DTBr C对这些蛋白的作用活性强于茶氨酸。DTBr C作用机制可能与抑制MDA-MB-231细胞VEGFR2-Akt信号传导通路相关。本研究结果提示,DTBr C可能具有广泛应用于临床治疗和(或)辅助治疗高转移乳腺癌的潜力。
In order to improve the activity of theanine and to develop a new antitumor drug, a new theanine derivative, tea dibromoamide (DTBr C), was synthesized. The theanine and the tea dibromoamide were compared to highly metastatic human breast cancer Inhibition of MDA-MB-231 Cell Growth and Its Molecular Mechanism. The effect of different concentrations of DTBr C on the growth of MDA-MB-231 cells was detected by MTT method. The expression of proteins closely related to apoptosis and growth in MDA-MB-231 cells and the potential target of the drug were analyzed by Western blot . The results showed that DTBr C inhibited the growth of MDA-MB-231 cells more than its parent compound theanine. DTBr C significantly decreased the level of anti-apoptotic protein Bcl-2 and greatly increased the expression of pro-apoptotic protein Bax, -2 / Bax ratio. In addition, DTBr C significantly inhibited the expression and phosphorylation of vascular endothelial growth factor receptor VEGFR2 and protein kinase Akt. DTBr C had stronger activity on these proteins than theanine. The mechanism of DTBr C may be related to the inhibition of VEGFR2-Akt signaling pathway in MDA-MB-231 cells. The results of this study suggest that DTBr C may have the potential to be widely used in clinical treatment and / or adjuvant therapy for highly metastatic breast cancer.