Lin J, Chen L-Y, Lin Z-X, Zhao M-L
College of Life Science and Biotechnology, Jiaotong University, Shanghai, China.
J Int Med Res. 2007 Sep-Oct;35(5):637-43. doi: 10.1177/147323000703500508.
Triptolide, derived from the traditional Chinese herb, Tripterygium wilfordii, sensitizes cancer cells to apoptosis. Glioblastoma multiforme (GBM), which accounts for most cases of central nervous malignancy, has a very poor prognosis and lacks effective therapeutic inventions. We, therefore, investigated the effects of different concentrations of, and different periods of exposure to, triptolide on cell proliferation and apoptosis in the glioma cell lines, U251MG and U87MG, and in normal human fetal astrocytes. Cell proliferation was investigated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and growth curve analysis, and apoptosis was assessed from genomic DNA fragmentation. Triptolide showed dose-dependent inhibition of cell proliferation and induction of apoptosis in glioma cells. It also increased the ratio of the pro-apoptotic protein, Bax, to the anti-apoptotic protein, Bcl-2. Since U87MG has the wild-type p53 gene whereas U251MG harbours a mutated p53 gene, our results indicate that triptolide induces apoptosis in GBM cells via a p53-independent pathway. The dose-dependent inhibition of cell proliferation and induction of apoptosis by triptolide may involve upregulation of Bax and downregulation of Bcl-2.
雷公藤甲素源自传统中药雷公藤，可使癌细胞对凋亡敏感。多形性胶质母细胞瘤（GBM）占中枢神经系统恶性肿瘤的大多数病例，预后很差且缺乏有效的治疗方法。因此，我们研究了不同浓度和不同暴露时间的雷公藤甲素对胶质瘤细胞系U251MG和U87MG以及正常人胎儿星形胶质细胞的细胞增殖和凋亡的影响。通过MTT（3-[4,5-二甲基噻唑-2-基]-2,5-二苯基溴化四氮唑）试验和生长曲线分析研究细胞增殖，并通过基因组DNA片段化评估凋亡。雷公藤甲素在胶质瘤细胞中显示出剂量依赖性的细胞增殖抑制和凋亡诱导作用。它还增加了促凋亡蛋白Bax与抗凋亡蛋白Bcl-2的比率。由于U87MG具有野生型p53基因，而U251MG含有突变的p53基因，我们的结果表明雷公藤甲素通过p53非依赖性途径诱导GBM细胞凋亡。雷公藤甲素剂量依赖性的细胞增殖抑制和凋亡诱导可能涉及Bax的上调和Bcl-2的下调。
