摘要
目的探讨血府逐瘀汤对非小细胞肺癌荷瘤小鼠糖原合成酶激酶3β(GSK-3β)与β-连环蛋白(β-catenin)表达的影响。方法采用右侧腋皮下接种人非小细胞肺癌A549细胞方法制备荷瘤小鼠模型,将造模成功的32只小鼠随机分为4组,每组8只。所有小鼠均腹腔注射5 mL/kg生理盐水,模型组、血府逐瘀汤低剂量组、血府逐瘀汤中剂量组、血府逐瘀汤高剂量组再分别灌胃蒸馏水5 mL/kg、血府逐瘀汤12.5 g/kg、血府逐瘀汤25 g/kg、血府逐瘀汤50 g/kg,均1次/d,连续灌胃14 d。灌胃结束后测量各组小鼠瘤重,计算肿瘤体积和生长抑制率;采用流式细胞仪检测各组肿瘤组织细胞凋亡率;分别采用Western blot和qTR-PCR法检测各组肿瘤组织中GSK-3β和β-catenin蛋白及mRNA表达情况。结果血府逐瘀汤各剂量组瘤重、肿瘤体积均明显低于模型组(P均<0.05);血府逐瘀汤各剂量组瘤重、肿瘤体积呈剂量依赖性降低,生长抑制率呈剂量依赖性增高,各剂量组间两两比较差异均有统计学意义(P均<0.05)。血府逐瘀汤各剂量组细胞凋亡率和肿瘤组织中GSK-3β蛋白及mRNA相对表达量均明显高于模型组(P均<0.05),β-catenin蛋白及mRNA相对表达量均明显低于模型组(P均<0.05);血府逐瘀汤各剂量组细胞凋亡率和肿瘤组织中GSK-3β蛋白及mRNA相对表达量呈剂量依赖性增高,β-catenin蛋白及mRNA相对表达量呈剂量依赖性降低,各剂量组间两两比较差异均有统计学意义(P均<0.05)。结论血府逐瘀汤能够有效抑制非小细胞肺癌荷瘤小鼠肿瘤组织生长,促进肿瘤细胞凋亡,其可能通过上调GSK-3β表达和下调β-catenin表达,抑制Wnt/β-catenin信号通路活性发挥抗肿瘤作用,且随着血府逐瘀汤剂量增加作用越明显。
Objective It is to investigate the effect of Xuefu Zhuyu Decoction on the expression of glycogen synthase kinase 3β(GSK-3β)andβ-catenin in tumor-bearing mice with non-small cell lung cancer(NSCLC).Methods The tumor-bearing mouse model was established by subcutaneously inoculating human non-small cell lung cancer A549 cells in the right armpit.The 32 mice that were successfully modeled were randomly divided into 4 groups with 8 mice in each group.All the mice received intraperitoneal injection of 5 mL/kg normal saline,and the model group,Xuefu Zhuyu Decoction low dose group,Xuefu Zhuyu Decoction medium dose group,and Xuefu Zhuyu Decoction high dose group were respectively given distilled water 5 mL/kg,Xuefu Zhuyu Decoction 12.5 g/kg,25 g/kg,50 g/kg,all once per day,continuously treated for 14 days.After treatment,the tumor weight of all the mice was measured,tumor volume and growth inhibition rate were calculated.Flow cytometry was used to detect the apoptosis rate of tumor tissue in each group;Western blot and qTR-PCR were used to detect the protein and mRNA expression of GSK-3βandβ-catenin in tumor tissue of each group.Results The tumor weight and tumor volume in each dose group of Xuefu Zhuyu Decoction were significantly lower than those in the model group(all P<0.05).The tumor weight and tumor volume decreased in a dose-dependent manner,while the growth inhibition rate increased in a dose-dependent manner in each dose group of Xuefu Zhuyu Decoction,the differences between each dose group were significant(P>0.05).The apoptosis rate and the relative expression of GSK-3βprotein and mRNA in tumor tissue in each does groups of Xuefu Zhuyu Decoction were significantly higher than those in the model group(all P<0.05),while the relative expression ofβ-catenin protein and mRNA were significantly lower than those in the model group(all P<0.05);the apoptosis rate and the relative expression of GSK-3βprotein and mRNA in tumor tissue increased in a dose-dependent manner,and the relative expression ofβ-catenin prot
作者
王理槐
孙银辉
张领兄
刘欢
周琴
袁苏云
张亚茹
朱乐
张红
WANG Lihuai;SUN Yinhui;ZHANG Lingxiong;LIU Huan;ZHOU Qin;YUAN Suyun;ZHANG Yaru;ZHU Le;ZHANG Hong(The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha 410007, Hunan, China;Hunan University of Traditional Chinese Medicine, Changsha 410208, Hunan, China;Chongqing Jiulongpo District Hospital of Traditional Chinese Medicine, Chongqing 400000, China)
出处
《现代中西医结合杂志》
CAS
2022年第5期603-607,共5页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
湖南省自然科学基金项目(2020JJ4485)。
