肠胃清介导CXCR4/CXCL12信号转导通路干预小鼠结肠癌肝转移

目的:观察中药复方肠胃清对小鼠结肠癌肝转移的抑制作用,从趋化因子受体4(CXCR4)/趋化因子12(CXCL12)信号转导通路及基质金属蛋白酶9(MMP9)的表达探讨肠胃清抑制结肠癌肝转移的作用机制。方法:采用原位瘤块接种法建立小鼠结肠腺癌细胞CT26肝转移模型,实验共分为4组,即假手术组、模型组、肠胃清低剂量组和高剂量组。假手术组和模型组均给予生理盐水,肠胃清低、高剂量组小鼠每日给药量分别为10.37,20.74 g·kg-1。HE染色法判断肝转移;免疫组织化学和实时荧光定量PCR实验方法检测CXCR4,CXCL12和MMP9的表达。结果:肠胃清低、高剂量组小鼠结肠癌原位瘤的质量抑制率分别为24.73%,45.91%;体积抑制率分别为27.93%,63.48%。模型组与肠胃清低、高剂量组肝转移率分别为75%,37.5%,12.5%。模型组结肠癌组织中CXCR4,CXCL12,MMP9的蛋白和mRNA表达显著高于假手术组(P<0.05);与模型组比较,肠胃清低剂量组和高剂量组CXCR4的蛋白和mRNA表达显著减低(P<0.05);肠胃清低剂量组和高剂量组CXCL12的蛋白表达显著降低(P<0.05);肠胃清高剂量组CXCL12的mRNA表达显著降低(P<0.05);肠胃清高剂量组MMP9的蛋白和mRNA表达显著降低(P<0.05)。结论:肠胃清抑制小鼠结肠癌原位瘤的生长和肝转移的发生率,肠胃清抑制结肠癌肝转移可能与其下调小鼠结肠癌原位瘤组织中CXCR4,CXCL12,MMP9的表达有关。

Changweiqing Cediates CXCR4/CXCL12 Signal Pathway to Intervene Liver Metastasis of Colorectal Cancer in Mice

Objective: To observe the inhibitory effect of Changweiqing on liver metastasis of colorectal cancer in mice, and investigate the related mechanism of Changweiqing on liver metastases of colorectal cancer, by Chemokine Ligand 12 (CXCL12)/Chemokine Receptor 4 (CXCR4)the signal transduction pathway and the expression of Matrix metalloproteinase 9(MMP9). Method: We established the liver metastases model of mice with implanted colon cancer CT26.Mice were divided into four groups, namely sham operation group, model group, the low dose group and the high dose group of Changweiqing. Sham operation group and model group were given normal saline, Changweiqing low and high dose groups were administrated with 10.37,20.74 g·kg^-1 respectively. The HE staining was performed to judge liver metastasis. The expression of the CXCR4, CXCL12, and MMP9 was detected by immunohistochemistry and quantitative real-time PCR in the colorectal tumor tissues and the normal colon tissue. Result: The weight inhibition rates of colon in situ tumor in Changweiqing low and high dose groups were 24.73%, 45.91%; while the volume inhibition rates were 27.93%, 63.48%. The liver metastasis rates were 75%, 37.5%, 12.5% in the model group, Changweiqing low and high dose groups respectively. The CXCR4, CXCL12, MMP9 protein and mRNA expression of the colon tumor tissue in model group were significantly higher than that in the sham operation group (P<0.05), while the low and high dose Changweiqing could reduce their expressions (P<0.05). CXCR4 protein and mRNA expression in Changweiqing low dose and high dose groups showed significant decrease compared with those in model group (P<0.05). CXCL12, protein expression in Changweiqing low dose and high dose groups was significantly decreased compared with that in the model group (P<0.05). CXCL12 mRNA in Changweiqng high dose group was significantly decreased compared with that in the model group (P<0.05). For MMP9 protein and mRNA expression, Changweiqing high dose could decrease them significantly compared with those in the model group (P<0.05). Conclusion: Changweiqing inhibits the colorectal cancer tumor growth in situ and the incidence of liver metastasis in mice, The mechanism is likely related to the down-regulation of CXCR4, CXCL12, MMP9 expression in the tumor tissue.