新型基质金属蛋白酶抑制剂LY52对肝癌细胞株MMPs表达及体外侵袭能力的影响  

Influence of Neotype Matrix Metalloproteinase Inhibitor LY52 on Matrix Metalloproteinase Expression and Invasion in Vitro of Hepatocellular Carcinoma Cell Line

作　　者：赵新[1,2] 许焕丽[3] 唐伟[3] 国土典宏[3] 董家鸿[1] 

机构地区：[1]解放军总医院肝胆外科,北京100853 [2]解放军302医院肝胆外科,北京100039 [3]东京大学医学部附属病院肝胆胰外科

出　　处：《中国普外基础与临床杂志》2010年第8期798-802,共5页Chinese Journal of Bases and Clinics In General Surgery

基　　金：日本厚生省助成基金资助

摘　　要：目的探讨新型基质金属蛋白酶(MMP)抑制剂LY52对人肝癌细胞HepG2中MMPs表达及细胞侵袭能力的影响。方法应用MTT比色法观察不同浓度的LY52作用不同时间对HepG2细胞增殖的影响;应用明胶酶谱分析方法观察不同浓度的LY52作用24h对HepG2细胞分泌MMPs的影响,并进一步应用Western blot法检测HepG2细胞中MMP-2蛋白的表达;应用侵袭小室检测不同浓度LY52作用后HepG2细胞侵袭能力的改变。结果在较低药物浓度(<200μg/ml)下,LY52对HepG2细胞无明显抗增殖作用或毒性作用;明胶酶谱分析及Western blot检测结果提示LY52能够显著抑制人肝癌细胞HepG2中MMP-2的表达及活性,其抑制效果呈剂量依赖性逐渐增强;随LY52药物浓度的增加,其抑制肝癌细胞侵袭能力也逐渐增强。结论 LY52能够通过抑制MMP-2的活性及表达,抑制肝癌细胞HepG2的侵袭能力;LY52可作为一种有潜力的抗肿瘤侵袭药物值得进一步研究。Objective To examine the effects of newly designed LY52 on the expression of matrix metalloproteinases and invasive ability of hepatocellular carcinoma HepG2 cells. Methods The effects of LY52 on the proliferations of HepG2 cells were detected by MTT assay. Gelatin zymography and Western blot were used to detect the effects of LY52 on matrix metalloproteinase-2 expression in the cell line. Transwell chamber assay was used to detect the effects of LY52 on the invasion of the cells. Results No obvious inhibitory or cytotoxicity effects of LY52 was found in lower concentrations （200 μg/ml） of LY52. Gelatin zymography and Western blot showed that matrix metalloproteinase-2 expression were inhibited by LY52 in a dose-dependent manner in HepG2 cells. Furthermore,transwell chamber assay showed that LY52 could significantly inhibit the invasion of the cell line in a dose-dependent manner. Conclusion The results suggest that LY52 may inhibit the invasion of hepatocellular carcinoma cells by suppressing the matrix metalloproteinase-2 activity.

关 键 词：LY52 肝细胞癌 基质金属蛋白酶 侵袭 

分 类 号：R735.7[医药卫生—肿瘤]