基质金属蛋白酶-2活性与成釉细胞瘤增殖生长关系的研究

Association of Matrix Metalloproteinase- 2 Activity with Cell Proliferation and Growth in Ameloblastoma

目的探讨基质金属蛋白酶-(2MMP-2)活性与成釉细胞瘤增殖生长的关系及其在成釉细胞瘤侵袭中的作用。方法通过MMP-2抑制剂Ro31-9790抑制MMP-2活性进行干预处理,采用成釉细胞瘤细胞原代培养、瘤组织块裸鼠肾包膜下移植、MTT、流式细胞术、瘤体积测量和组织学检查等方法,观察MMP-2活性与成釉细胞瘤增殖生长的关系。结果实验各组之间在同一时间点的细胞增殖活性均无显著性差异(P>0.05)。G0/G1、G2/M期细胞比率以及凋亡细胞比率不随Ro31-9790浓度增加而增加,S期细胞比率也不随Ro31-9790浓度增加而减少。Ro31-9790治疗组瘤体积明显小于对照组(P<0.05),瘤体积增加也明显少于对照组(P<0.01)。结论Ro31-9790对成釉细胞瘤细胞的体外增殖活性无影响,但可抑制体内移植瘤的生长,MMP-2活性与成釉细胞瘤细胞的增殖活性无关,但与成釉细胞瘤的生长密切相关,可能是成釉细胞瘤局部侵袭的机制之一。

Objective To investigate the relationship between matrix metalloproteinase-2 （MMP-2）activity and cell proliferation, growth and invasion of ameloblastoma. Methods The cells and xenograft of ameloblastoma were treated with MMP-2 inhibitor Ro31-9790 and the effects of Ro31-9790 on the cell proliferation and growth of ameloblastoma were observed. Primary culture in vitro, subcapsular kidney xenograft in vivo, MTY assay, flow cytometry, neoplasitc volume measurement and histochemistry were employed to study the effects of cell proliferation and growth produced by Ro31-9790. Results There was no significant different in cell proliferation at same interval among several groups （P〉0.05）. The ratio of G0/G1 stage, G2/M stage and apoptotic cells didn＇t increase following increased Ro31-9790, and the ratio of S stage cells also didn＇t reduce following increased Ro31-9790. The tumor volume and its increase in treatment group were significant less than those in control group. Conclusion Ro31-9790 does not influence proliferation of ameloblastoma cells in vitro, but it can effectively inhibit the ameloblastoma growth in vivo. MMP-2 activity has no relationship to proliferation of ameloblastoma cells, but it can contribute to the ameloblastoma growth and may be a reason of invasion in ameloblastoma.