苦参碱对人结肠癌细胞株HT-29肝转移潜能的抑制作用

目的研究苦参碱对人结肠癌细胞株HT-29肝转移能力的影响,并探讨其机制。方法HT-29细胞体外培养,以0、0.125、0.25、0.5mg/ml不同浓度苦参碱进行预处理48h后,采用半定量RT-PCR检测各组培养细胞乙酰肝素酶(Heparanase,HPSE)mRNA表达的变化,应用细胞黏附实验检测细胞黏附能力的改变,Transwell小室检测体外侵袭能力的变化;建立结肠癌肝转移模型,腹腔内注射不同浓度的苦参碱,6周后,处死裸鼠,计数肝转移率和肝转移结节数。结果与对照组比较,随着苦参碱浓度的增加,各浓度苦参碱处理组HT-29细胞HPSE mRNA的表达和细胞黏附侵袭能力均受到明显的抑制(P<0.01),各组转移率及转移鼠肝转移结节数目依次下降,差异有统计学意义(P<0.05)。结论苦参碱可以抑制结肠癌肝转移,且抑制作用呈剂量依赖性。机制可能与通过下调HT-29细胞HPSE mRNA的表达进而使结肠癌细胞黏附侵袭力降低有关。

Inhibition of liver metastasis of colon cancer cell line HT-29 by matrine

Objective To investigate the effect of matrine on the potential ability of liver metastasis of colon cancer line HT-29 and its mechanisms. Methods The HT-29 cells were treated by matrine in different concentration.The total RNAs were extracted from the cells 48 hours after treatment and then semi-quantitative RT-PCR were performed to evaluate the heparanase-mRNA(HPSE mRNA) expression levels.Effect of matrine on adhesion of treated HT-29 cells was tested by cell matrigel adhesion assay.Adhensive and invasive ability of HT-29 cells was measured by matrigel invasion assay.HT-29 cells were injected intrasplenically into BALB/c nude mice to produce diffuse liver metastasis.Mice were randomly divided into 0,0.125,0.25,0.5 mg/ml matrine treated groups.Animals were sacrificed after 6 weeks,and their livers were processed for histological examination.Liver metastatic rate and tumor foci in liver were counted.Results The hepanase-mRNA expression,adhesion and invasiveness in vitro of HT-29 cells treated with matrine of different final concentrations significantly decreased compared with that of the controls(P<0.01).Matrine displays a significant inhibitory effect on liver metastasis compared to the control(P<0.05).Conclusion By down-regulating the expression of heparanase-mRNA,matrine has a significant inhibitory effect on the adhesion and invasiveness of human colon cancer in vitro and liver metastasis in a dose dependent manner.