苦参碱对结肠癌肝转移小鼠SCAP/SREBP1信号通路的调节作用研究

Regulatory effect of matrine on SCAP/SREBP1 signal pathway in mice with liver metastasis of colon cancer

关键词:  苦参碱  结肠癌肝转移  SCAP/SREBP1信号通路

Key words:  matrine  liver metastasis of colon cancer  SCAP/SREBP1 signal pathway

摘要:

[目的] 研究苦参碱对结肠癌肝转移小鼠肿瘤抑制作用及对SCAP/SREBP1信号通路的调节作用。[方法] 72只小鼠随机分为空白对照组、肝转移模型组、苦参碱低、中、高剂量组及卡培他滨组，每组12只，采用脾内注射结肠癌HCT116细胞法建立结肠癌肝转移小鼠模型，苦参碱低、中、高剂量组分别灌胃给予12.5、25、50 mg/kg的苦参碱，给药21 d，卡培他滨组按照267 mg/kg灌胃给予卡培他滨，测定小鼠肝脏质量及肝转移结节数，酶联免疫吸附法（ELISA）测定肝组织转化生长因子β1蛋白（TGF-β1）、白介素（IL）-6水平，苏木精-伊红（HE）染色法检查肝组织病理学，实时定量聚合酶链式反应（PCR）测定肿瘤组织SCAP、SREBP1 mRNA水平，免疫印迹（Western blot）法测定肿瘤组织SCAP、SREBP1水平。[结果] 与空白对照组比较，肝转移模型组小鼠肝脏质量、肝转移结节数、肝组织TGF-β1及IL-6水平、肿瘤组织SCAP、SREBP1 mRNA及蛋白水平显著升高（P<0.05）；与肝转移模型组比较，苦参碱各剂量组肝脏质量、肝转移结节数、肝组织TGF-β1及IL-6水平、肿瘤组织SCAP、SREBP1 mRNA及蛋白水平显著降低（P<0.05），随着苦参碱剂量的增加，各项指标降低更明显。[结论] 苦参碱能够显著抑制结肠癌肝转移，缓解肝组织病理学改变，其机制可能与调节SCAP/SREBP1信号通路有关。

Abstract:

[Objective] To study the inhibitory effect of matrine on liver metastasis of colon cancer and its regulation on SCAP/SREBP1 signal pathway in mice. [Methods] The 72 mice were randomly divided into blank control group,liver metastasis model group,low,middle and high dose matrine groups and capecitabine group,with 12 mice in each group. The mouse model of colon cancer liver metastasis was established by intrasplenic injection of HCT116 cells. The low,middle and high dose matrine groups were given 12.5,25,50 mg/kg,for 21 days. Capecitabine group was given capecitabine by intragastric administration according to 267 mg/kg. The liver weight and the number of liver metastatic nodules were measured. The levels of transforming growth factor(TGF-β1) and interleukin (IL)-6 in liver tissue were measured by enzyme-linked immunosorbent assay (ELISA). Liver histopathology was examined by hematoxylin-eosin (HE) staining. The levels of SCAP and SREBP1 mRNA in tumor tissue were determined by real-time quantitative polymerase chain reaction (PCR). The levels of SCAP and SREBP1 in tumor tissue were determined by Western blot. [Results] Compared with the blank control group,the liver weight,the number of hepatic metastatic nodules,the levels of TGF-β1 and IL-6 in liver tissue,and the levels of SCAP,SREBP1 mRNA and protein in tumor tissue in liver metastasis model group were significantly higher than those in control group(P<0.05). Compared with the liver metastasis model group,the liver weight,the number of liver metastatic nodules,the levels of TGF-β1 and IL-6 in liver tissue,and the levels of SCAP,SREBP1 mRNA and protein in tumor tissue in each dose group were significantly lower than those in the liver metastasis model group(P<0.05). [Conclusion] Matrine can significantly inhibit liver metastasis of colon cancer and alleviate liver histopathological changes,and its mechanism may be related to the regulation of SCAP/SREBP1 signal pathway.