肾上腺素促进胶质母细胞瘤细胞的增殖、迁徙和侵袭及其潜在机制

目的 探讨肾上腺素对胶质母细胞瘤细胞系U87MG和U251增殖、迁徙和侵袭的影响。方法用 不同浓度的肾上腺素(0.1、1、10、50、100 μmol/L)处理U87MG和U251胶质母细胞瘤细胞株,分别采用MTT实验、细胞划痕实验和transwell侵袭实验观察细胞的增殖、迁徙和侵袭情况。所有实验均以不加肾上腺素处理的细胞为对照组。qRT-PCR、Western blot和明胶酶谱法检测基质金属蛋白酶-9 (matrix metalloproteinase-9,MMP-9)的表达和活性。结果 与空白对照相比,肾上腺素能促进U251的增殖,促进U87MG和U251的迁徙和侵袭能力,且具有剂量依赖性;β肾上腺素能受体(β adrenoreceptor,β-AR)阻滞剂普萘洛尔能抑制肾上腺素促进胶质母细胞瘤细胞迁徙和侵袭的作用;MMP-9表达和活性随着肾上腺素浓度升高而增加。结论 肾上腺素能促进胶质母细胞瘤细胞的增殖、迁徙和侵袭,这种效应可能和MMP-9的表达增加相关,且能被β-AR阻滞剂抑制。

Epinephrine increases proliferation,migration and invasion of human glioblastoma cell cultures and its potential mechanism

Objective To investigate the effects of epinephrine on the proliferation, migration and invasion of the glioblastoma cell lines U87MG and U251. Methods The U87MG and U251 glioblastoma cell lines were treated with various concentrations of epinephrine (0.1, 1, 10, 50, 100 μmol/L). MTT assay, scratch wound healing assay and transwell invasion assay were used to investigate cell proliferation, migration and invasion, respectively. Cells treated without epinephrine were set as control group for the above assays. Gelatin zymography, qRT-PCR and Western blot were used to determine the activity and the expression of matrix metalloproteinase-9 (MMP-9). Results Following treatment with epinephrine, the proliferation of U251 and the migration and invasion of both U87MG and U251 were significantly increased compared with that of the blank control group. Furthermore, a dose-dependent association was identified between the effect and epinephrine dose. Propranolol, a kind of β adrenoreceptor (β-AR) blocker, could reverse the effect of epinephrine on U87MG and U251 glioblastoma cell lines. The expression and activity of MMP-9 was significantly increased and affected by raising of epinephrine dose. Conclusions Epinephrine treatment could stimulate proliferation, migration and invasion of human glioblastoma cells, which may related to the increase of MMP-9 expression, and could be reversed by β-AR blockers.