基质金属蛋白酶抑制剂对胶质瘤细胞和胶质瘤干细胞体外侵袭抑制作用的比较

Effects of matrix metalloproteinase inhibitor on invasiveness of glioma cells in vitro

目的 观察基质金属蛋白酶（MMP）抑制剂对常规贴壁培养的人脑胶质瘤细胞和胶质瘤干细胞侵袭能力的影响及两者间的差异.方法 应用一种三维胶原凝胶侵袭模型,将常规贴壁培养的胶质瘤细胞与无血清、悬浮细胞球条件下培养的胶质瘤干细胞（1. 0×104～1.5×104个/样本）分别接种于该模型中,加入不同浓度的MMP抑制剂GM6001（0、25、50、75、100 μmol/L）培养4 d,通过观察各组细胞侵袭距离及其差异,判断该抑制剂对两种细胞侵袭能力的影响及差异.结果 两组细胞对GM6001的抑制作用表现出不同程度的剂量依赖性,75μmol/L GM6001对常规培养的胶质瘤细胞侵袭抑制最明显,而25 μmol/L GM6001对胶质瘤干细胞的侵袭抑制最显著.结论 MMP抑制剂在体外对胶质瘤细胞具有侵袭抑制作用,胶质瘤干细胞显示出对MMP抑制剂更高的敏感性.

Objective To investigate the differenct effects of matrix metalloproteinase （MMP） inhibitor on invasiveness of adherently cultured differentiated human glioma cells and human glioma stem cells. Methods The spheres formed by hanging drops from adherent glioma cells and glioma stem cells neurospheres （1.0 × 104-1.5 × 104 cells/sample） were planted respectively into gelatum models and cultured in the medium with MMP inhibitor at different concentrations （0, 25, 50, 75, 100 μmol/L）. The distance of cells migration of the two groups was measured after culture for 4 days and analyzed by SPSS.Results Cells grew well in gelatum models and invaded in the gelatum ridically with time. The inhibitory effects of GM6001 on invasiveness of the two groups were distinctive and showed a dose-dependent manner compared with the controls. GM6001 at 75 μmol/L had the greatest inhibitory effect on human glioma differentiated cells, whereas at 25 μmol/L on human glioma stem cells. Conclusion The inhibitory effects of GM6001 on invasiveness of human glioma cells are dose-dependent, which may play two opposite roles in the treatment of glioma.