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- 2018
mTOR抑制剂联合替莫唑胺治疗恶性胶质瘤
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Abstract:
摘要 目的： 研究mTOR抑制剂替西罗莫司(Temsirolimus)联合替莫唑胺(Temozolomide)对C6鼠胶质瘤增殖及侵袭的影响.方法: 传代培养C6大鼠胶质瘤细胞,HE染色观察细胞形态的变化,MTT比色法检测药物对C6细胞的体外增殖抑制作用.原位注射法建立C6大鼠胶质瘤模型,10 d后分为替西罗莫司组、替莫唑胺组、联合药物组(替西罗莫司+替莫唑胺)及空白组,隔天给药7次,4周后断头法处死大鼠取脑,做肿瘤病理组织切片,计算肿瘤体积;TUNEL法检测肿瘤细胞凋亡指数,检测与肿瘤侵袭性有关的MMP1(基质金属蛋白酶1)的表达.结果: 联合药物组促进肿瘤细胞凋亡效果显著高于替莫唑胺组(P<0.01).与空白组比较,替莫唑胺组移植瘤体积下降了33.5%(P<0.05),移植瘤中MMPl表达为(++),移植瘤细胞凋亡率64.6%(P<0.05);联合药物组移植瘤体积下降了55.2%(P<0.05),移植瘤中MMPl表达阳性(+),细胞凋亡率 84.0%(P<0.05).结论: 西罗莫司联合替莫唑胺用药能明显抑制C6大鼠胶质瘤细胞移植瘤生长,并降低与肿瘤侵袭能力有关的MMP1蛋白表达.
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