山楂多糖提取物上调miR-146a-5p抑制Wnt/β-catenin信号通路影响胃癌细胞增殖和凋亡  

Up-regulation of miR-146a-5p by Hawthorn polysaccharide extract inhibits Wnt/β-catenin signaling pathway to affect proliferation and apoptosis of gastric cancer cells

作　　者：李孝平 李伟 高芳芳 黄朝刚 何天佑 孙智珺 LI Xiaoping;LI Wei;GAO Fangfang;HUANG Chaogang;HE Tianyou;SUN Zhijun(Department of General Surgery,Wuhan Third Hospital,Wuhan,Hubei 430060,China)

机构地区：[1]武汉市第三医院普外科,湖北武汉430060

出　　处：《安徽医药》2021年第2期326-330,共5页Anhui Medical and Pharmaceutical Journal

摘　　要：目的探讨山楂多糖提取物对胃癌细胞增殖和凋亡的影响及机制。方法用浓度分别为200、400、800μg/mL的山楂多糖提取物处理AGS细胞,作为不同浓度山楂多糖提取物组;正常培养的细胞作为对照(NC)组;用800μg/mL的甘露醇处理作等渗对照,记为800μg/mL甘露醇组。将miR-NC、miR-146a-5p转染至AGS细胞中记为miR-NC组、miR-146a-5p组;将anti-miRNC、anti-miR-146a-5p转染至AGS细胞中再用浓度为800μg/mL的山楂多糖提取物处理,记为anti-miR-NC+山楂多糖提取物组、anti-miR-146a-5p+山楂多糖提取物组。四甲基偶氮唑盐比色法(MTT)检测细胞增殖率;流式细胞术检测细胞凋亡;实时荧光定量PCR(RT-qPCR)检测miR-146a-5p表达水平。结果与对照组(100.10±10.02)%相比,200、400、800μg/mL山楂多糖提取物组胃癌细胞AGS的增殖率(85.12±8.51)%、(68.22±6.82)%和(42.11±4.21)%降低(F=31.314,P<0.05)。不同浓度山楂多糖提取物处理的胃癌细胞AGS中细胞增殖率降低,细胞凋亡率升高,miR-146a-5p表达水平升高(P<0.05)。高表达miR-146a-5p,细胞增殖率降低,细胞凋亡率升高(P<0.05)。低表达miR-146a-5p部分逆转了山楂多糖提取物对胃癌细胞AGS增殖和凋亡的影响。山楂多糖提取物处理的胃癌细胞AGS中β-catenin表达水平降低,低表达miR-146a-5p逆转了山楂多糖提取物对β-catenin表达的抑制作用。结论山楂多糖提取物可抑制胃癌细胞AGS增殖,促进细胞凋亡,其机制可能与miR-146a-5p和Wnt/β-catenin信号通路有关。Objective To investigate the effect and mechanism of polysaccharide extract of Cornus officinalis on proliferation and apoptosis of gastric cancer cells.Methods AGS cells were treated with hawthorn polysaccharide extracts at concentrations of 200,400,and 800μg/mL,respectively,as different concentrations of hawthorn polysaccharide extract group;normal cultured cells were used as control(NC)group,treated with 800μg/mL mannitol as an isotonic control,recorded as 800μg/mL mannitol group.miR-NC and miR-146 a-5 p were transfected into AGS cells and recorded as miR-NC group and miR-146 a-5 p group;anti-miR-NC and anti-miR-146 a-5 p were transfected into AGS cells and treated with hawthorn polysaccharide extract at a concentration of 800μg/mL,and recorded as an anti-miR-NC+hawthorn polysaccharide extract group and an anti-miR-146 a-5 p+hawthorn polysaccharide extract group.Cell proliferation rate was detected by MTT assay;apoptosis was detected by flow cytometry;real-time quantitative PCR(RT-qPCR)was used to detect the expression of miR-146 a-5 p.Results The cell proliferation rate of gastric cancer cells AGS treated with different concentrations of hawthorn polysaccharide extract was decreased[(100.10±10.02)%vs.(85.42±8.51)%,(68.22±6.82)%,(42.11±4.21)%,P<0.05],the apoptosis rate was increased,and the expression of miR-146 a-5 p was increased(P<0.05).High expression of miR-146 a-5 p,cell proliferation rate was decreased,apoptosis rate was increased(P<0.05).Low expression of miR-146 a-5 p partially reversed the effect of hawthorn polysaccharide extract on proliferation and apoptosis of gastric cancer cell AGS.The expression ofβ-catenin in gastric cancer cells AGS treated with polysaccharide extract of hawthorn was decreased,the low expression of miR-146 a-5 p reversed the inhibitory effect of hawthorn polysaccharide extract onβ-catenin expression.Conclusions Hawthorn polysaccharide extract can inhibit the proliferation of gastric cancer cells AGS and promote cell apoptosis.The mechanism may be related to miR-146

关 键 词：山楂属 植物提取物 miR-146a-5p WNT/Β-CATENIN信号通路 胃癌 增殖 凋亡 

分 类 号：R285.5[医药卫生—中药学]