加味小陷胸汤对接种人胃癌SGC-7901裸鼠移植瘤生长及Wnt/β-catenin信号通路相关蛋白表达的影响

Effect of Jiawei Xiaoxianxiong Decoction on the Growth of Xenograft Tumor and the Expression of Wnt/β-catenin Signaling Pathway Proteins in Nude Mice Inoculated with Human Gastric Cancer SGC-7901 Cells

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.