Inhibition Of Growth On Human Glioma Cells By Estramustiene Anti-Microtubule Agent ; In Vitro Study

雌莫司烯抗微管剂对人神经胶质瘤细胞生长的抑制；

基本信息

批准号：
07671548
负责人：
YOSHIDA Daizo
金额：
$ 1.34万
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：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671548/
关键词：
Estramustine glioma Matrigel matrix metalloproteinase tumor invasion 細胞浸潤 Cell invasion matrix metallo proteinase microtubule Matrigel glioma MTT assay zymogram グリオーマ glioma collagenase metalloproreiase

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 invasicveness. To determine whrther 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 eatramustine 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オM,compared with the control group. On the haptoinvasion assay, no statistically significant difference was seen in the 0.5オM estramustine group, while 1 to 10オM estramustine groups revealed significant suppression of invasion from 6 to 24 hours in a dode-dependent manner. The results syggest 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 treafment of this disease.

由于微管是细胞运动性和细胞内转运的重要组成部分，因此合理提出抗微管剂，雌激素对神经胶质瘤微管的解聚作用会调节细胞入侵剂。为了确定金属蛋白酶（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，Zymogram图，胶原溶解测定和抗抗毒性测定的影响。 Zymogram图表明，随着Eatramustine浓度的增加，基质金属蛋白酶2的激活（62KD）形式。与对照组相比，胶原蛋白分解测定法证明，雌马司氨酸以剂量依赖性方式抑制酶活性的酶活性速率约为2.5至21倍，与对照组相比。在抗抗性测定法上，在0.5 O M雌激素组中没有看到统计学上的显着差异，而1至10 O M雌激素组显示出以DODE依赖性方式对6至24小时的侵袭显着抑制。雌激素的结果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。恶性神经胶质瘤细胞浸润能力的抑制可能在该疾病的宝藏中具有重要价值。