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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 investigate the effect of LY52, a novel matrix metalloproteinase (MMP) inhibitor, on the expression of MMPs and the invasion ability of HepG2 cells. Methods MTT assay was used to observe the effects of different concentrations of LY52 on the proliferation of HepG2 cells. Gelatin zymography was used to observe the effect of different concentrations of LY52 on the secretion of MMPs by HepG2 cells. Western blot was used to detect the expression of HepG2 The expression of MMP-2 protein in cells was detected. Invasion chamber was used to detect the invasion ability of HepG2 cells after treated with different concentrations of LY52. Results LY52 had no obvious anti-proliferative effect or toxicity on HepG2 cells at lower drug concentration (<200μg / ml). Gelatin zymography and Western blot showed that LY52 could significantly inhibit the expression of MMP-2 in HepG2 cells Expression and activity, the inhibitory effect in a dose-dependent manner gradually increased; with the concentration of LY52 drug, its ability to inhibit the invasion of hepatocellular carcinoma also gradually increased. Conclusion LY52 can inhibit the invasion ability of HepG2 cells by inhibiting the activity and expression of MMP-2. LY52 can be used as a potential antitumor drug for further study.