3种环六缩酯肽类化合物体外抑制人食管癌活性的研究

IN VITRO STUDY IN ANTI-HUMAN ESOPHAGEAL CARCINOMA ACTIVITY OF THREE CYCLOPEPTIDES COMPOUNDS

目的检测3种环六缩酯肽类化合物对人食管癌细胞增殖活性的影响,初步探讨化合物结构与活性之间的关系。方法利用溴化噻唑蓝四氮唑[3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyhetrazoliumbromide,MTT]比色法检测3种环肽类化合物抑制人食管癌细胞增殖活性的影响。结果 Pullularin C对2种试验用人食管癌细胞[人食管癌高度分化细胞(T-Tn)和人食管癌中低度分化细胞(TE-2)]均显示极强的抑制作用,尤其是对T-Tn细胞的增殖的半数抑制浓度仅为65.12nmol/L,强于阳性对照紫杉醇和顺铂;而结构相似的化合物[Phe3,N-MeVal5]Destruxin B和Pseudodestruxin C对T-Tn和TE-2细胞的增殖显示中等程度抑制活性或不显示抑制活性。结论Pullularin C对2种试验用人食管癌细胞均显示极强的抑制作用;[Phe^3,N-MeVal^5]Destruxin B和Pseudodestruxin C均属于Destruxin类的19元环六缩酯肽化合物,而Pullularin C属于18元环六缩酯肽化合物,基本骨架不同可能是造成它们活性差别很大的原因。

Objective To detect the anti-human esophageal cancer cells effect of three cyclopeptides compounds, and to explore the relationship among the structures and activity. Methods The effects of three cyclopeptides compounds on human esophageal cancer cells were determined by 3- （4,5-dimethyhhiazol-2-yl） -2,5-diphenyltetrazoliumbromide（MTI＇） assay in vitro. Results Pullularin C exhibited significant anti-growth activities to human esophageal cancer cell, and 50% inhibitory Concentration（ IC50 ） value of T-Tn cell was 65.12nmol/L exposure. [ Phe3, N-MeVal5] destruxin B and pseudodestruxin C demonstrated weak anti-growth activities to T-Tn and TE-2 cell lines even in the concentration of 〉 100mol/L. Conclusion Pullularin C exhibited significant anti-growth activities to human esophageal cancer cells. These results clearly suggested that the anti-tumor activities were closely related to the structures of cyclopeptides： inactive two cyclopeptides were 19-membered macro- cyclopeptides, while active one was 18-membered macro-cveloDeotide.