新型基质金属蛋白酶抑制剂LY52对肝癌细胞HepG2.2.15体外侵袭能力的影响  

Effect of matrix metalloproteinase inhibitor LY52 on the invasion ability of hepatocellular carcinoma cell line HepG2.2.15

作　　者：赵新[1] 董磊[2] 洪智贤[1] 张克明[1] 肖朝辉[1] 张绍庚[1] 唐伟[3] 

机构地区：[1]解放军第三〇二医院肝胆外科一中心,北京100039 [2]空军总医院临床检验中心,北京100142 [3]东京大学医学部附属病院肝胆胰外科

出　　处：《传染病信息》2012年第5期269-272,共4页Infectious Disease Information

基　　金：日本厚生省助成基金(CDTTR200804)

摘　　要：目的研究新型基质金属蛋白酶(matrix metalloproteinases,MMP)抑制剂LY52对转染HBV的肝癌细胞HepG2.2.15中MMP的表达及细胞侵袭能力的影响。方法用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐细胞增殖检测试剂盒测定LY52对细胞增殖的影响;用明胶酶谱分析法研究药物对MMP-2及MMP-9表达的影响,并进一步应用蛋白印迹(Westernblotting,WB)杂交检测MMP-2蛋白表达的改变。用侵袭小室法检测药物作用后肿瘤细胞侵袭能力的改变。结果 LY52能够抑制肿瘤细胞的增殖;明胶酶谱法和WB杂交提示HepG2.2.15细胞表达较高水平的MMP-2和MMP-9;LY52作用后,HepG2.2.15细胞的MMP-2表达受到显著抑制,而MMP-9表达的抑制作用不明显,且HepG2.2.15细胞体外侵袭能力明显降低。结论 LY52能够通过抑制MMP-2的活性及表达,抑制肝癌细胞HepG2.2.15的侵袭能力。LY52作为有潜力的抗肿瘤侵袭药物值得进一步研究。Objective To investigate the effect of matrix metalloproteinase （MMP） inhibitor LY52 on the expression of MMP and the invasion ability of HBV-transfected hepatocellular carcinoma （HCC） cell line HepG2.2.15. Methods The effect of LY52 on the proliferation of HepG2.2.15 cells was detected by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyhetrazolium bromide assay, on the expression of MMP-2 and MMP-9 was detected by using gelatin zymography, on the expression of MMP-2 protein was detected by using Western blotting, and on the invasion abilities of the cells was detected by using transwell invasion assay. Results The cell proliferation was inhibited by LY52. Gelatin zymography and Western blotting showed that MMP-2 and MMP-9 were highly expressed in HepG2.2.15 cells. As the concentration of LY52 increased, the expression of MMP-2 was more obviously inhibited, while that of MMP-9 was not. Furthermore, transwell invasion assay showed that LY52 could significantly inhibit the invasion of HepG2.2.15 cell line. Conclusions LY52 may inhibit the invasion of HepG2.2.15 cells by suppressing the activity and expression of MMP-2. As a potential agent to suppress tumor invasion, LY52 is worthy of further research.

关 键 词：吡咯烷类 癌 肝细胞 HEPG2细胞 基质金属蛋白酶9 基质金属蛋白酶2 

分 类 号：R735.7[医药卫生—肿瘤]