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首页> 外文期刊>Neurosurgery >Inhibition of glioma angiogenesis and invasion by SI-27, an anti-matrix metalloproteinase agent in a rat brain tumor model.
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Inhibition of glioma angiogenesis and invasion by SI-27, an anti-matrix metalloproteinase agent in a rat brain tumor model.

机译：SI-27是一种抗基质金属蛋白酶试剂，可在大鼠脑肿瘤模型中抑制神经胶质瘤的血管生成和侵袭。

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OBJECTIVE: The matrix metalloproteinase (MMP) inhibitor SI-27 has undergone extensive development because of its effectiveness against glioma invasion and angiogenesis. However, previous studies have been performed in vitro. The present work investigates the potential of SI-27 to inhibit tumor invasion, slow angiogenesis, and prolong survival in rodent brain tumor models. METHODS: Stable enhanced green fluorescent protein-expressing clones of a human malignant glioma cell line, U251MG, were stereotactically xenografted into the periphery of the anterior striatum and corpus callosum of Fischer 944 rats after immunosuppression with cyclosporin A. SI-27 (1 or 10 mg/kg) or carrier solution was administered on three successive days by intraperitoneal injection, and tumor invasion and angiogenesis were assessed 3 weeks later by quantitative image analysis. This was performed on whole brain sections analyzed either by direct observation of enhanced green fluorescent protein-expressing glioma cells or by additional immunohistochemistry to detect the endothelial cells with anti-factor VIII monoclonal antibody. In situ zymography on frozen sections was used to detect MMP activity. RESULTS: The group receiving a total of 30 mg/kg showed a statistically significant (P < 0.001) increase in survival time compared with the controls receiving carrier (median survival, 47.3 versus 32.6 d). There was also a decrease in MMP activity, tumor cell invasion, and neovascularization. In contrast, animals given 3 mg/kg did not show these differences. CONCLUSION: Systemic administration of the anti-MMP agent SI-27 is effective in the treatment of glioma in an animal model.
机译：目的：基质金属蛋白酶（MMP）抑制剂SI-27由于其抗神经胶质瘤侵袭和血管生成的作用而得到了广泛的发展。但是，先前的研究已经在体外进行。本工作研究了SI-27在啮齿类脑肿瘤模型中抑制肿瘤入侵，减缓血管生成和延长生存期的潜力。方法：用环孢菌素A. SI-27免疫抑制后，将人恶性神经胶质瘤细胞系U251MG稳定表达绿色荧光蛋白的克隆U251MG立体定向异种移植到Fischer 944大鼠的前纹状体和体周围。通过腹膜内注射连续三天给药（mg / kg）或载体溶液，并在3周后通过定量图像分析评估肿瘤的侵袭和血管生成。通过直接观察表达增强型绿色荧光蛋白的神经胶质瘤细胞或通过额外的免疫组织化学法用抗因子VIII单克隆抗体检测内皮细胞，对全脑切片进行分析。冷冻切片上的原位酶谱法用于检测MMP活性。结果：与接受载体的对照组相比，总共接受30 mg / kg的组的生存时间有统计学上显着的增加（P <0.001）（中位生存期分别为47.3和32.6 d）。 MMP活性，肿瘤细胞侵袭和新血管形成也降低。相反，给予3 mg / kg的动物没有显示出这些差异。结论：抗MMP药物SI-27的全身给药可有效治疗动物模型中的神经胶质瘤。

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