Inhibition of Growth on Human Glioma Cells by Estramustiene, Anti-microtubule Agent ; In Vitro Study

抗微管剂雌莫司烯对人胶质瘤细胞生长的抑制作用；

基本信息

批准号：
11671398
负责人：
YOSHIDA Daizo
金额：
$ 1.02万
依托单位：
Nippon Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Because microtubules are important components of cell motility and intracellular transport, it is reasonable to propose that an antimicrotubule agent, estramustine's depolymerizing effect on glioma microtubules would modulate cell invasiveness. To determine whether matrix metalloproteinases, key factors in cell invasion, are affected by exposure to estramustine, a cell proliferation assay, a zymogram, a collagenolysis assay, and a haptoinvasion assay were employed in this study. The zymogram revealed that an activated (62kD) form of Matrix Metalloproteinase-2 diminished with increasing estramustine concentrations. The collagenolysis assay demonstrated approximately 2.5 to 21 fold lower rates of enzymatic activity suppressed by estramustine in a dose-dependent manner at estramustine concentrations of 1, 5, and 10 μM, compared with the control group. On the haptoinvasion assay, no statistically significant difference was seen in the 0.5 μM estramustine group, while 1 to 10 μM estramustine groups revealed significant suppression of invasion from 6 to 24 hours in a dose-dependent manner. The results suggest that estramustine suppresses the invasion of U87MG cells in vitro by the decreasing available matrix metalloproteinase-2, an affect caused by the disassembly of microtubules. Suppression of the infiltrative capacity of malignant glioma cells could be of significant value in the treatment of this disease.

由于微管是细胞运动和细胞内转运的重要组成部分，因此可以合理地提出，抗微管剂，雌司氨酸对神经胶质瘤微管的解聚作用会调节细胞侵袭性。为了确定基质金属蛋白酶（细胞浸润中的关键因素）是否受到暴露于雌激素的影响，细胞增殖测定法，Zymogram，Zymogram，胶原分解测定和抗抗毒性测定在这项研究中。 Zymogram图显示，随着雌激素浓度的增加，基质金属蛋白酶2的激活（62KD）形式减少。与对照组相比，胶原蛋白分解测定法显示，雌马司氨酸以剂量依赖性方式抑制了雌激素的酶活性速率约2.5至21倍，与对照组相比。在抗染色测定中，在0.5μM雌激素组中没有看到统计学上的显着差异，而1至10μM雌激素基团显示出以剂量依赖性方式从6到24小时的侵袭显着抑制。结果表明，雌激素通过降低可用的基质金属蛋白酶-2抑制了U87MG细胞的侵袭，这是由微管的拆卸引起的。抑制恶性神经胶质瘤细胞的浸润能力对于该疾病的治疗可能具有重要价值。