摘要
目的探讨褐藻聚合酚(PFFE-A)对大肠癌细胞增殖与侵袭的影响,以及其对转化生长因子β_(1)(TGF-β_(1))及母体抗生物皮肤生长因子同源物2/3(Smad2/3)通路的调控作用。方法细胞分组:依次以50、100、150μmol·L-1的小、中、大剂量的PFFE-A干预细胞,另设立正常对照组细胞。5-乙炔基-2'脱氧尿苷(EdU)染色检测细胞的增殖;Transwell小室检测细胞的侵袭能力;异种种植结肠癌裸鼠模型检测细胞的体内生长与转移能力;实时荧光定量聚合酶链反应(RT-qPCR)检测细胞中上皮间质转化(EMT)相关基因的表达;Western blotting检测细胞中TGF-β_(1)、p-Smad2/3的表达水平。结果与正常对照组比较,PFFE-A小、中、大剂量组细胞的增殖率、侵袭细胞数、肿瘤瘤体质量、病灶转移比例、神经型钙黏附蛋白(N-cadherin)的mRNA的表达、TGF-β_(1)和p-Smad2/3的表达明显下降(P<0.05),E-钙黏蛋白(E-cadherin)的mRNA的表达明显升高(P<0.05),具有明显的剂量依赖性(P<0.05)。结论PFFE-A能抑制肿瘤细胞的EMT过程,抑制大肠癌细胞HT29的体外增殖与侵袭能力,下调其体内生长与转移的能力,这可能是通过下调TGF-β_(1)/Smads信号实现的。
Objective To investigate the effect of phlorofucofuroeckol A(PFFE-A)on the proliferation and invasion of colorectal carcinoma cells and its regulation of transforming growth factor-β_(1)(TGF-β_(1))and mothers against decapentaplegic homolog 2/3(Smad2/3)signaling pathway.Methods The cells were processed as follows:the cells were intervened with low,medium and high doses of 50,100,and 150μmol·L-1 of PFFE-A,respectively and cells in the normal control group were also established.5-Ethynyl-2'-deoxyuridine(EdU)staining was used to detect the cell proliferation.The transwell chamber was used to detect the invasion ability.A xenograft colon cancer nude mice model was used to detect the growth and metastasis ability of the cells in vivo.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of epithelial-to-mesenchymal transition(EMT)related genes.Western blotting was used to detect the expression levels of TGF-β_(1) and p-Smad2/3 in cells.Results Compared with normal control group,the proliferation rate,the number of invaded cells,the tumor mass,the proportion of tumor metastasis,the expression of N-cadherin mRNA,the expression of TGF-β_(1) and p-Smad2/3 were significantly decreased(P<0.05),and the mRNA expression of E-cadherin was significantly increased(P<0.05).All were presented with a significant dose-dependent(P<0.05).Conclusion PFFE-A could inhibit the EMT process of tumor cells,inhibit the proliferation and invasion of HT29 cells in vitro,and down-regulate the growth and metastasis of HT29 cells in vivo,which may be achieved by down-regulating TGF-β_(1)/Smad2/3 signaling pathway.
作者
李红
董玮
侯杰
贺德
LI Hong;DONG Wei;HOU Jie;HE De(Department of General Surgery,Baoan District People's Hospital,Shenzhen 518000,China)
出处
《医药导报》
CAS
北大核心
2024年第4期495-501,共7页
Herald of Medicine
基金
深圳市宝安区医疗卫生基础研究(非资助)项目(DH654165215633)。
