摘要
目的:研究加味小陷胸汤对人胃癌MGC803细胞上皮间质转化(EMT)抑制作用及与分泌型糖蛋白Wnt/β-连环蛋白(Wnt/β-catenin)通路关系。方法:采用人胃癌MGC803细胞悬液种植法构建BALB/c裸鼠皮下异位移植性肿瘤动物模型。造模成功后随机分为模型组、加味小陷胸汤低、中、高剂量组(16.0,32.0,64.0 g·kg^(-1)),卡培他滨组(400 mg·kg^(-1)),每组8只,灌胃给药,每日1次,连续给药28 d,其中卡培他滨组给2周停1周。观察裸鼠一般状态、体质量,测量移植瘤大小,处死后称质量并计算抑瘤率;苏木素-伊红(HE)染色法观察移植瘤组织病理学变化;用实时荧光定量聚合酶链式反应(Real-time PCR),蛋白免疫印迹法(Western blot)检测Wnt1,β-catenin的基因和蛋白表达水平及Western blot检测基质金属蛋白酶-9(MMP-9),血管内皮生长因子(VEGF),N-钙黏蛋白(N-cadherin),E-钙黏蛋白(E-cadherin),波形蛋白(Vimentin),锌指蛋白(Snail)蛋白表达水平;酶联免疫吸附测定(ELISA)检测环氧合酶2(COX2),前列腺素E;(PGE;)的表达水平。结果:各组移植瘤体积随时间呈现不同的增长趋势,模型组增长趋势最为明显,与模型组比较,加味小陷胸汤低、中、高剂量组、卡培他滨组瘤体积呈现不同程度的生长抑制、增长趋势降低,且随时间延长作用明显,给药7,14,21,28 d加味小陷胸汤低、高剂量组、卡培他滨组移植瘤体积明显降低(P<0.05,P<0.01),给药14,21,28 d加味小陷胸汤中剂量组移植瘤体积显著降低(P<0.01)。与模型组比较,给药7,14,21,28 d,加味小陷胸汤高剂量组、卡培他滨组裸鼠移植瘤相对肿瘤体积显著降低(P<0.01),给药14,21,28 d,加味小陷胸汤低、中剂量组移植瘤相对肿瘤体积明显降低(P<0.05,P<0.01)。与模型组比较,加味小陷胸汤低、中、高剂量组、卡培他滨组移植瘤抑瘤率显著升高(P<0.01)。与模型组比较,加味小陷胸汤中低、中、高剂量组、卡培他滨组均能下调瘤组�
Objective:To observe the inhibitory effect of modified Xiao Xianxiongtang on epithelialmesenchymal transition(EMT)of human gastric cancer MGC803 cells and its relationship with secretory glycoprotein Wnt/β-catenin pathway.Method:The BALB/c nude mice were implanted with human gastric cancer MGC803 cell suspension in the heterotopic subcutaneous position for inducing tumor.After successful modeling,they were randomly divided into the model group,low-,medium-,and high-dose(16.0,32.0,and64.0 g·kg^(-1)) groups of modified Xiao Xianxiongtang,and capecitabine(400 mg·kg^(-1)) group,with eight mice in each group,and gavaged with the corresponding drugs,once per day,for 28 consecutive days.Those in the capecitabine group received one-week discontinuation after every two weeks of treatment.The general state and body weight of the nude mice were observed,and the transplanted tumor volume was measured.After being killed,they were weighed and the tumor inhibition rate was calculated.Hematoxylin-eosin(HE)staining was carried out for observing the pathological changes in transplanted tumor tissues.The gene and protein expression levels of Wnt1 andβ-catenin were detected by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)and Western blot,followed by the determination of matrix metalloproteinase-9(MMP-9),vascular endothelial growth factor(VEGF),N-cadherin,E-cadherin,Vimentin,and Snail protein expression by Western blot.The expression levels of cyclooxygenase 2(COX2)and prostaglandin E;(PGE;)were detected by enzyme-linked immunosorbent assay(ELISA).Result:It was found that the transplanted tumor in each group showed different growth trends with time,with the most obvious growth observed in the model group.Compared with the model group,the low-,medium-,and high-dose modified Xiao Xianxiongtang groups exhibited reduced tumor volume and slowed growth to varying degrees over time.After medication for days 7,14,21,and 28,the tumor volumes in the low-and high-dose modified Xiao Xianxiongtang groups and cap
作者
谷金繁
王翔
陈建
汤同娟
左梦雨
洪星辉
王靓
黄金玲
GU Jin-fan;WANG Xiang;CHEN Jian;TANG Tong-juan;ZUO Meng-yu;HONG Xing-hui;WANG Liang;HUANG Jin-ling(Anhui University of Chinese Medicine,Hefei 230012,China;Institute of Integrated Traditional Chinese and Western Medicine,Anhui Academy of Chinese Medicine,Hefei 230012,China;Anhui Province Key Laboratory of Chinese Medicinal Formula,Hefei 230012,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2022年第4期42-50,共9页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金面上项目(81573864)。
关键词
加味小陷胸汤
胃癌
移植瘤
上皮间质化
分泌型糖蛋白Wnt/β-连环蛋白
modified Xiao Xianxiongtang
gastric cancer
transplanted tumor
epithelial-mesenchymal transition(EMT)
secretory glycoprotein Wnt/β-catenin
