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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和细胞内运输的重要组成部分，因此有理由提出，抗微管剂雌莫司汀对胶质瘤微管的解聚作用将调节细胞侵袭性。为了确定基质金属蛋白酶，在细胞侵袭的关键因素，暴露于雌莫司汀的影响，细胞增殖试验，酶谱，胶原溶解试验，和haptoinvasion试验在这项研究中。酶谱显示，活化的（62 kD）形式的基质金属蛋白酶-2减少与Eatramustine浓度的增加。胶原溶解试验表明，与对照组相比，雌莫司汀浓度为1、5和10 μ M时，雌莫司汀以剂量依赖性方式抑制酶活性的速率降低约2.5至21倍。在接触侵袭试验中，0.5 μ M雌莫司汀组无统计学显著性差异，而1 - 10 μ M雌莫司汀组在6 - 24小时内以剂量依赖性方式显著抑制侵袭。结果提示雌莫司汀可能通过减少微管的解聚而降低基质金属蛋白酶-2的活性，从而抑制U87 MG细胞的体外侵袭能力。抑制恶性胶质瘤细胞的浸润能力对治疗本病有重要价值。