环六缩酚肽化合物体外抑制人肺癌细胞增殖活性及其机制的研究

IN VITRO ANTI -HUMAN LUNG TUMOR ACTIVITY AND MECHANISM STUDIES OF THREE CYCLIC HEXADEPSIPEPTIDES

目的检测3种环六缩酚肽化合物对人肺部肿瘤细胞增殖活性的影响,并初步探讨其可能的作用机制。方法腐败菌素B,pseudodestruxin C和pullularin C在3种浓度100,10和1μmol/L分别作用于人非小细胞肺癌细胞(A549和QC-56)和人小细胞肺癌细胞(PC-6和QG-90),MTT比色法检测细胞存活率,计算IC_(50)。腐败菌素B,pseudodestruxin C和pullularin C在浓度1μmoL/L时作用于A549细胞24h,双荧光素酶报告基因检测系统检测p53报告基因(pG53-Luc)、bax报告基因(pGBax-Luc)、核因子-kB报告基因(Igk-Luc)和激活T细胞核因子报告基因(NFAT-Lue)的表达。结果 pullularin C对4种实验用人肺癌细胞均显示极强的抑制作用,强于阳性对照药物顺铂;而结构相似的化合物腐败菌素B和pseudodestruxin C对实验用人肺部肿瘤细胞的增殖不显示抑制活性。结论环六缩酚肽化合物pullularin C对人肺癌细胞的增殖具有较强的抑制活性,并且1μmol/L.pullularinC可明显诱导A549细胞内p-53和bax基因转录的表达,推测pullularin C对人肺肿瘤细胞增殖的抑制作用可能是通过诱导肿瘤细胞凋亡来实现的。

Objective To study the anti - human lung tumor effect of three cyclic hexadepsipeptides and to explore their mechanism. Methods The anti - human lung tumor effect of destruxin B,pseudodestruxin C and pullularin C were investigated using non -small -cell lung cancer cells（ A549 and QG -96 ）and small cell lung cancer cells （PC -6 and QG -90 ）. The cell viabilities were examined by MTI＇ assay. A549 cell line was transiently cotransfected by pG53 - Luc,pGBax - Luc, Igk - Luc and NFAT - Luc reporter plasmid and SV - 40 - Rluc plasmid. The effects of three cyclic hexadepsipeptides of luciferase activity expression were detected by Dual - Luciferase Reporter Assays. Results Pullularin C exhibited significantly anti -growth activities to human lung cancers. Destruxin Band pseudodestruxin C demonstrated weak anti -growth activities to cell lines even in the concentration of more than 100 μmol/L. The reporter gene of pGBax - Luc and pG53 - Luc were observed in response to pullularin C. Conclusion Pullularin C has significant anti - growth activities in human lung cancer cells. The possible mechanism of the anti - growth activities to human lung cancers cytotoxicity of pullularin C is through inducing human lung cancer cell apoptosis.