去甲肾上腺素对胶质母细胞瘤侵袭迁移能力的影响及机制研究

目的   研究应激激素去甲肾上腺素(NE)对胶质母细胞瘤侵袭迁移能力的影响及机制，并探讨β受体阻断剂普萘洛尔(propranolol)抗应激所致肿瘤侵袭转移的可行性。方法   培养胶质母细胞瘤细胞系T98G、U251及U87，采用RT-PCR检测胶质瘤细胞系β肾上腺素能受体表达，Transwell评价NE对胶质瘤细胞侵袭迁移的影响，明胶酶谱法检测NE对胶质瘤细胞系MMP 2分泌水平影响。结果   随NE浓度增加(0.1~10μmol/L)，胶质瘤细胞侵袭力逐渐增强(P>0.05)，普萘洛尔(1nmol/L)可抑制此效应；随NE浓度增加(0.1~10μmol/L)，胶质瘤细胞基质金属蛋白酶 2(MMP-2)分泌显著增多，普萘洛尔(1nmol/L)可抑制NE诱导的MMP 2分泌。结论   应激激素去甲肾上腺素可以促进胶质母细胞瘤MMP-2分泌酶活性从而增强其迁移能力，普萘洛尔可以抑制NE诱导的胶质瘤侵袭增强。

The effect and mechanism of norepinephrine on glioblastoma invasion

Objective   To investgate the effect and mechanism of norepinephrine(NE) on glioblastoma invasion and migration, and to evaluate the possibility of β-blocker propranolol as an anti-invasion agent. Methods   RT-PCR was performed to detect the expression of β-adrenergic receptors in T98G, U251 and U87 cell lines. Transwell assay was performed to evaluate the effect of NE on glioblastoma invasion. Gelatin zymography was used to assess the effect of NE on MMP-2 activity in glioblastoma. Results   Compared with the control group, NE (0.1μmol/L~10μmol/L) significantly induced glioblastoma cell invasion. The β-receptor antagonist propranolol (1nmol/L) could block the NE induced glioblastoma invasion. The activity of  MMP-2 increased significantly after NE (0.1μmol/L~10μmol/L) stimulation, which could be abrogated by propranolol (1nmol/L). Conclusion   NE can promote MMP-2 secretion in glioblastoma to facilitate its invasion, which can be inhibited by Propranolol.