茶氨酸硝香酰胺对人宫颈癌细胞生长的抑制作用

Inhibitory effects of TNC against in vitro and in vivo growth of human cervical cancer cells

前期研究发现本试验合成的茶氨酸衍生物茶氨酸硝香酰胺(TNC)具有显著抑制人肺癌细胞体内外生长的作用,为进一步探索研究TNC的抗癌活性和作用的分子机制,以其母体化合物茶氨酸为对照,评估现TNC对人宫颈癌细胞生长的抑制作用。采用MTT方法检测不同浓度的TNC对人宫颈癌细胞生长的影响,应用蛋白质印迹法检测解析这些癌细胞中与凋亡和生长密切相关蛋白的表达和药物可能作用的分子靶点。此外,通过建立动物肿瘤模型,评价TNC对荷瘤裸鼠体内人宫颈癌He La肿瘤生长的抑制效果。实验结果显示,TNC抑制人宫颈癌细胞体内外生长的活性超过其母体化合物茶氨酸多倍,对小鼠生长无明显毒性;TNC抑制人宫颈癌细胞生长的分子机制可能与抑制VEGFR2-NF-κB信号传导通路相关。本研究结果提示,TNC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。

The purpose of this study is to investigate the inhibitory effects of TNC,a synthesized theanine derivative from our laboratory on the growth of human cervical cancer cells and the molecular mechanisms of action. The MTT assay was used to evaluate the effects of TNC on the growth of human cervical cancer cells. Western blotting was employed to analyze the protein expressions and the possible molecular targets of action related to the growth inhibition and apoptosis in the cervical cancer cells treated with TNC. In addition, an animal tumor mode was established to assess the inhibitory effects of TNC on human cervical tumor growth in tumor-bearing nude mice. The experimental results show that TNC has enhanced the growth inhibition of the cervical cancer cells and cervical tumor by multifold as compared with theanine without detectable toxicity to the mice. Suppression of VEGFR2 and NF-κB signaling pathway may be the important molecular mechanism of TNC＇s and theanine＇s action against the growth of human cervical cancer cells. Our results suggest that TNC may have the therapeutic and/or adjuvant therapeutic application in the treatment of human cervical cancer.