Thrombin enhances glioma growth.
Thrombin enhances glioma growth.
复制标题
凝血酶促进神经胶质瘤的生长。
DOI：
10.1007/978-3-211-85578-2_69
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Muraszko,KarinM
中科院分区：
文献类型：
--
作者：
Hua,Ya;Tang,Lingling;Keep,RichardF;Hoff,JulianT;Heth,Jason;Xi,Guohua;Muraszko,KarinM
背景我们的前期研究表明，阿加曲班，一种特异性凝血酶抑制剂，可以减轻大鼠胶质瘤模型的脑水肿和神经功能缺损。本研究探讨凝血酶是否能促进胶质瘤的生长。方法本研究分为两部分。在第一部分中，大鼠C6胶质瘤细胞用或不用凝血酶处理。然后将这些细胞注射到成年雄性Fischer 344大鼠的右尾状核中。在12天后处死大鼠之前进行行为测试以测量肿瘤质量。在第二部分中，将C6细胞在无血清培养基中孵育24小时，然后用凝血酶处理，加或不加阿加曲班（一种凝血酶抑制剂）。用5-溴-2 ′-脱氧尿苷（BrdU）ELISA试剂盒检测DNA合成。使用3-（4，5-二甲基噻唑-2-基）-2，5-二苯基-四唑溴化物（MTT）assay.FindingsTreatment的C6细胞与凝血酶脑内植入导致在一个更大的肿瘤质量和更糟糕的神经功能缺损在第12天。在体外，凝血酶增加C6胶质瘤细胞的DNA合成，这种作用被阿加曲班阻断。MTT法显示凝血酶可显著增加胶质瘤细胞的体外增殖。ConclusionsIn summary，凝血酶可增强C6胶质瘤的体内生长和体外细胞增殖，提示凝血酶可能是胶质瘤治疗的靶点。
BackgroundOur previous studies have demonstrated that argatroban, a specific thrombin inhibitor, reduces brain edema and neurological deficits in rat glioma models. The present study investigated whether or not thrombin enhances glioma growth in vivo and in vitroMethodsThere were two parts in this study. In the first part, rat C6 glioma cells were treated with or without thrombin. These cells were then injected into the right caudate of adult male Fischer 344 rats. Rats underwent behavioral testing prior to sacrifice 12 days later for tumor mass measurement. In the second part, C6 cells were incubated in serum-free medium for 24 hours and then treated with thrombin with or without argatroban, a thrombin inhibitor. DNA synthesis was examined using a 5-bromo-2′-deoxyuridine (BrdU) ELISA kit. Cell proliferation was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay.FindingsTreatment of C6 cells with thrombin prior to intracerebral implantation resulted in a larger tumor mass and worse neurological deficits at day12. In vitro, thrombin increased DNA synthesis in C6 glioma cells, and this effect was blocked by argatroban. MTT assay showed that thrombin significantly increased glioma cell proliferation in vitro.ConclusionsIn summary, thrombin enhances C6 glioma growth in vivo and cell proliferation in vitro suggesting that thrombin may be a target of glioma therapy.