Lin J, Chen L, Lin Z, Zhao M
College of Life Science and Biotechnology, Jiaotong University, Shanghai, People's Republic of China.
J Int Med Res. 2007 Jul-Aug;35(4):490-6. doi: 10.1177/147323000703500408.
This study investigated the effect of triptolide, derived from the traditional Chinese herb Tripterygium wilfordii, on the growth of glioblastoma multiforme (GBM) cells. Glioma cell lines U251MG and U87MG and normal human fetal astrocytes were exposed to various concentrations of triptolide, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium and colony formation assays were used to measure cell growth and survival. Cell apoptosis was determined using annexin V. Levels of the oncogenic transformation-related proteins Ras-guanosine triphosphate (Ras-GTP), extracellular signal-regulated kinase (ERK) and Akt were determined by Western blotting. Triptolide caused a dose-dependent decrease in proliferation and increase in apoptosis in the glioma cell lines. Since U87MG has a wildtype p53 gene while U251MG harbours a mutated p53 gene, these results indicate that triptolide induces apoptosis in GBM cells via a p53-independent pathway. Treatment of GBM cells with triptolide attenuated both the Ras/ERK and the Ras/Akt signalling pathways. This could provide a theoretical basis for triptolide treatment in GBM, but further animal studies and clinical research are necessary.
本研究调查了从传统中药雷公藤中提取的雷公藤内酯醇对多形性胶质母细胞瘤（GBM）细胞生长的影响。将胶质瘤细胞系U251MG和U87MG以及正常人胎儿星形胶质细胞暴露于不同浓度的雷公藤内酯醇中，并采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和集落形成试验来检测细胞生长和存活情况。使用膜联蛋白V测定细胞凋亡。通过蛋白质免疫印迹法测定致癌转化相关蛋白Ras-鸟苷三磷酸（Ras-GTP）、细胞外信号调节激酶（ERK）和Akt的水平。雷公藤内酯醇导致胶质瘤细胞系的增殖呈剂量依赖性降低，凋亡增加。由于U87MG具有野生型p53基因，而U251MG含有突变的p53基因，这些结果表明雷公藤内酯醇通过p53非依赖性途径诱导GBM细胞凋亡。用雷公藤内酯醇处理GBM细胞可减弱Ras/ERK和Ras/Akt信号通路。这可为雷公藤内酯醇治疗GBM提供理论依据，但还需要进一步的动物研究和临床研究。
