蓝萼甲素诱导胶质瘤细胞凋亡及其上调GEF-H1的作用机制

Mechanism of glaucocalyxin A that induces apoptosis of glioma cell and up-regulates GEF-H1

蓝萼香茶菜[Rabdosia japonica (Burm. f.) Hara var. glaucocalyx (Maxim.) Hara]是中国民间草药,具有抗肿瘤活性。此研究的目的是探讨蓝萼甲素(glaucocalyxin A,GLA),一种从蓝萼香茶菜中分离纯化得到的二萜类化合物,诱导胶质瘤细胞凋亡的作用及其机制。通过检测C6大鼠胶质瘤细胞的存活率及干扰核糖核酸(ribonucleic acid,RNA)、聚合酶链式反应(polymerase chain reaction,PCR)和蛋白质免疫印迹(Westernblot)技术以探究细胞凋亡的分子信号机制。当GLA存在时,C6大鼠胶质瘤细胞的存活率明显降低,鸟嘌呤核苷酸交换因子H1(guanine nucleotide-exchange factor,GEF-H1)表达上调,引起细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)蛋白磷酸化,造成细胞凋亡。因此,GLA诱导神经胶质细胞凋亡是通过激活GEF-H1/ERK途径。

Rabdosia japonica（Burm.f.） Hara var.glaucocalyx（Maxim.） Hara is a traditional Chinese medicine,and is known to have anti-tumor effects.This study aims to investigate the effect of glaucocalyxin A（GLA）,a diterpenoids extracted from Glaucocalyx Hara,on apoptosis of glioma cells and its mechanism.This study investigated the molecular signaling mechanism of GLA-induced glioma cell apoptosis by analyzing survival rate of C6 rat glioma cells,cell morphology,colony formation ability,interference ribonucleic acid,polymerase chain reaction,and Western blot.The result showed that in the presentce of GLA,the survival rate of C6 rat glioma cells decreased significantly,while the expression of guanine nucleotide-exchange factor-H1 was up-regulated,causing phosphorylation of extracellular regulated protein kinases proteins and apoptosis.Hence,the mechanism of GLA-induced glioma cell apoptosis was the GEF-H1/ERK pathway.