Yoshida D, Piepmeier J M, Bergenheim T, Henriksson R, Teramoto A
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.
Br J Cancer. 1998;77(1):21-5. doi: 10.1038/bjc.1998.4.
Because microtubules are important components of cell motility and intracellular transport, it is reasonable to propose that the depolymerizing effect of an antimicrotubule agent, estramustine, 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 used in this study. The zymogram revealed that an activated (62 kDa) 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 microM, compared with the control group. On the haptoinvasion assay, no statistically significant difference was seen in the 0.5 microM estramustine group, whereas 1-10 microM estramustine groups revealed significant suppression of invasion from 6 to 24 h in a dose-dependent manner. The results suggest that estramustine suppresses the invasion of U87MG cells in vitro using the decreasing available matrix metalloproteinase-2, an effect 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运输的重要组成部分，因此有理由认为抗微管药物雌莫司汀对胶质瘤微管的解聚作用会调节细胞侵袭性。为了确定细胞侵袭的关键因素基质金属蛋白酶是否受雌莫司汀暴露的影响，本研究采用了细胞增殖试验、酶谱分析、胶原酶解试验和透明质酸侵袭试验。酶谱分析显示，随着雌莫司汀浓度的增加，基质金属蛋白酶-2的活化形式（62 kDa）减少。胶原酶解试验表明，与对照组相比，在1、5和10 microM的雌莫司汀浓度下，雌莫司汀以剂量依赖的方式抑制酶活性的速率降低了约2.5至21倍。在透明质酸侵袭试验中，0.5 microM雌莫司汀组未见统计学显著差异，而1-10 microM雌莫司汀组在6至24小时内以剂量依赖的方式显示出对侵袭的显著抑制。结果表明，雌莫司汀通过减少可用的基质金属蛋白酶-2来抑制U87MG细胞在体外的侵袭，这种作用是由微管解聚引起的。抑制恶性胶质瘤细胞的浸润能力在该疾病的治疗中可能具有重要价值。
