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以茶氨酸为对照,探索研究以茶氨酸为原料合成的新的衍生物茶双溴香酰胺(DTBrC)对高转移的人宫颈癌细胞生长的抑制作用与其分子机制。采用MTT法检测不同浓度的DTBrC对人宫颈癌细胞生长的影响;应用蛋白质印迹法检测这些人宫颈癌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。结果显示,DTBrC抑制人宫颈癌细胞生长的活性超过其母体化合物茶氨酸7倍;DTBrC明显抑制血管内皮生长因子受体VEGFR2和转录因子NF-κB蛋白的表达,显著减少蛋白激酶Akt的表达和磷酸化水平,降低抗凋亡蛋白Bcl-2水平,提高促凋亡蛋白Bax表达,从而减少Bcl-2/Bax比率。DTBrC作用的分子机制可能与抑制VEGFR2-Akt/NF-κB信号传导通路相关。本研究结果提示,DTBrC具有应用于临床治疗和(或)辅助治疗高转移人宫颈癌的潜力。
Using theanine as a control, we investigated the inhibitory effect of DTBrC, a novel derivative of theanine, on the growth of highly metastatic human cervical carcinoma cells and its molecular mechanism. The effects of different concentrations of DTBrC on the growth of human cervical cancer cells were detected by MTT assay. The expressions of proteins closely related to apoptosis and growth in these human cervical cancer cells were detected by Western blotting and the possible targets of the drugs. The results showed that DTBrC inhibited the growth of human cervical cancer cells more than its parent compound theanine 7 times; DTBrC significantly inhibited vascular endothelial growth factor receptor VEGFR2 and transcription factor NF-κB protein expression, significantly reduced protein kinase Akt expression and Phosphorylation, decrease the level of anti-apoptotic protein Bcl-2 and increase the expression of pro-apoptotic protein Bax, thereby reducing the Bcl-2 / Bax ratio. The molecular mechanism of DTBrC may be related to the inhibition of VEGFR2-Akt / NF-κB signaling pathway. The results of this study suggest that DTBrC has the potential to be used clinically and / or adjuvantly in the treatment of highly metastatic human cervical cancer.