冬凌草乙素通过Wnt/β-catenin信号通路对裸鼠K562细胞移植瘤的抑制作用

摘要

目的 探讨单体化合物冬凌草乙素抑制K562细胞裸鼠皮下移植瘤的作用效果及可能的作用机制.方法 建立K562皮下移植瘤裸鼠动物模型20只,将其随机分为模型对照组、冬凌草乙素低、高剂量(40、80 mg/kg)组、阳性对照组(羟基脲120 mg/kg),每组5只,腹腔连续给药18d.每周测量各组裸鼠体质量和肿瘤体积,给药结束后处死动物并迅速取出肿瘤分析其抑瘤率.比较各组肿瘤组织中肿瘤细胞的凋亡和坏死情况;比较各组肿瘤组织中β-链蛋白(β-caterin)、细胞周期蛋白D1(cyclin D1)、c-myc癌基因的信使RNA表达水平及蛋白的表达情况.结果 冬凌草乙素能明显抑制裸鼠肿瘤生长体积,呈剂量依赖性并具有统计学意义(P＜0.01).冬凌草乙素组肿瘤细胞出现明显的凋亡和坏死现象.与模型对照组相比,冬凌草乙素组肿瘤组织β-链蛋白、cyclin D1和c-myc信使RNA的表达下调(P均＜0.05).与模型对照组相比,冬凌草乙素各剂量组均能下调肿瘤组织中的β-链蛋白、cyclin D1和c-myc蛋白的表达(P均＜0.05).结论 冬凌草乙素能够抑制K562细胞裸鼠移植瘤,其作用机制可能与抑制Wnt/β-catenin信号传导通路实现的.%Objective To investigate the inhibitory effect and underlying mechanism of monomer compound of ponicidin on K562 xenografted tumors in nude mice.Methods Twenty nude mouse models with subcutaneous K562 transplanted tumors were established and randomly divided into the control,low-dose ponicidin(40 mg/kg),high-dose ponicidin(80 mg/kg) and positive control groups(hydroxycarbamide,120 mg/kg;n =5 for each group).The medication was administered via intraperitoneal injection for consecutive 18 d.The weight of nude mice and the volume of tumors were measured weekly.All animals were sacrificed after medicine administration and the tumors were immediately removed to calculate the tumor-inhibitory rate.The apoptosis and necrosis of tumor cells were observed and statistically compared among four groups.The expression levels of the β-caterin,cyclin D1 and c-myc mRNA and proteins were quantitatively measured and statistically compared among four groups.Results Ponicidin could significantly suppress the growth of tumor in a dose-dependent manner (P ＜ 0.01).In the low-and high-dose ponicidin groups,evident apoptosis and necrosis of the tumor cells were seen.Compared with the control group,the expression levels of β-caterin,cyclin D1 and c-myc mRNA were significantly down-regulated (all P ＜ 0.05).Compared with the control group,the expression levels of β-caterin,cyclin D1 and c-myc proteins were significantly down-regulated in the low-and highdose ponicidin groups (all P ＜ 0.05).Conclusions Ponicidin can inhibit the growth of K562 transplanted tumors in nude mice,probably through suppressing the Wnt/β-catenin signaling transduction pathway.