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作 者:程楠[1] 王靓[1,2] 施慧 丁芮 洪星辉 方海雁 王恩宇 黄金玲 CHENG Nan;WANG Jing;SHI Hui;DING Rui;HONG Xing-hui;FANG Hai-yan;WANG En-yu;HUANG Jin-ling(School of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine, Anhui Hefei 230012, China;Anhui Provincial Key Laboratory of Traditional Chinese Medicine Compounds, Anhui Hefei 230012, China;School of Nursing, Anhui University of Chinese Medicine, Anhui Hefei 230012, China;The Affiliated Hospital of University of Science and Technology of China, Anhui Hefei 230001, China)
机构地区:[1]安徽中医药大学中西医结合学院,安徽合肥230012 [2]复方中药安徽省重点实验室,安徽合肥230012 [3]安徽中医药大学护理学院,安徽合肥230012 [4]中国科学技术大学附属医院,安徽合肥230001
出 处:《安徽中医药大学学报》2022年第2期82-87,共6页Journal of Anhui University of Chinese Medicine
基 金:国家自然科学基金项目(81173171,81573864)。
摘 要:目的观察加味小陷胸汤抑制人胃癌细胞株SGC-7901裸鼠皮下移植瘤生长作用,以及对Wnt/β-catenin信号通路相关蛋白和基因表达的影响,探讨加味小陷胸汤抗胃癌侵袭转移作用的分子机制。方法构建人胃癌细胞SGC-7901裸鼠皮下移植瘤模型。药物连续干预4周动态观察移植瘤体积变化,4周后剖取瘤组织称质量,采用Western blot法检测瘤组织β-连环蛋白(β-catenin)、糖原合成酶激酶-3(glycogen synthase kinase-3,GSK-3β)、原癌基因蛋白(cellular-myelocytomatosis viral oncogene,c-Myc)和血管内皮生长因子(vascular endothelial growth factor,VEGF)蛋白表达水平;采用RT-qPCR检测β-catenin、GSK-3βmRNA表达水平。结果与模型组比较,加味小陷胸汤各剂量组可显著降低SGC-7901胃癌移植瘤模型裸鼠皮下移植瘤体积和质量(P<0.05),能显著抑制移植瘤组织β-catenin、c-Myc、VEGF蛋白和β-catenin mRNA表达(P<0.05),上调GSK-3β蛋白和mRNA的表达水平(P<0.05),降低基质金属蛋白酶(matrix metalloproteinase,MMP)-2、MMP-9含量(P<0.05)。结论加味小陷胸汤能够有效抑制人胃癌细胞SGC-7901裸鼠皮下移植瘤的生长,并且可以调控与胃癌侵袭转移密切相关Wnt/β-catenin通路的过度激活。Objective To investigate the inhibitory effect of Jiawei Xiaoxianxiong Decoction on the growth of subcutaneous xenograft tumor in nude mice inoculated with human gastric cancer SGC-7901 cells,the effect of Jiawei Xiaoxianxiong Decoction on the expression of proteins and genes associated with the Wnt/β-catenin signaling pathway,and the molecular mechanism of Jiawei Xiaoxianxiong Decoction in inhibiting the invasion and metastasis of gastric cancer.Methods A model of subcutaneous xenograft tumor of human gastric cancer SGC-7901 cells was established in nude mice.The change in xenograft tumor volume was dynamically observed during the intervention for 4 consecutive weeks,and xenograft tumor tissue was collected and weighed.Western blot was used to measure the protein expression levels ofβ-catenin,glycogen synthase kinase-3β(GSK-3β),c-Myc,and vascular endothelial growth factor(VEGF)in xenograft tumor tissue,and RT-qPCR was used to measure the mRNA expression levels ofβ-catenin and GSK-3β.Results Compared with the model group,the Jiawei Xiaoxianxiong Decoction groups had significant reductionsin the volume and weight of xenograft tumor of gastric cancer SGC-7901 cells(P<0.05),significant reductions in the protein expression levels ofβ-catenin,c-Myc,and VEGF and the mRNA expression level ofβ-catenin(P<0.05),significant increases in the protein and mRNA expression levels of GSK-3β(P<0.05),and significant reductions in the content of MMP-2 and MMP-9(P<0.05).Conclusion Jiawei Xiaoxianxiong Decoction can effectively inhibit the growth of xenograft tumor of gastric cancer SGC-7901 cells in nude mice and regulate the overactivation of the Wnt/β-catenin pathway closely associated with the invasion and metastasis of gastric cancer.
关 键 词:加味小陷胸汤 胃癌 WNT/Β-CATENIN信号通路 移植瘤
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