Department of Obstetrics and Gynecology, Oita University Faculty of Medicine, Oita, Japan.
Cancer Lett. 2010 Nov 28;297(2):198-206. doi: 10.1016/j.canlet.2010.05.012. Epub 2010 Jun 14.
Triptolide (TPL), a bioactive component of the Chinese medicinal herb Tripterygium wilfordii Hook F, induces apoptosis in some lines of human tumor cells. However, the effect of TPL on gynecologic cancer cells has not yet been well-described. We investigated the effects of TPL on cell growth, cell cycle, and apoptosis in endometrial and ovarian cancer cell lines. Furthermore, we examined global changes in gene expression after treatment with TPL. By using a list of 20 differentially expressed genes, Western blot analyses were performed on five endometrial and ovarian cancer cell lines. All cell lines were sensitive to the growth-inhibitory effect of TPL. TPL increased the proportion of cells in the S-phase of the cell cycle and induced apoptosis. cDNA microarray assay demonstrated that the treatment with TPL changed the expression of cell cycle regulators, apoptosis-related factors and cell proliferation markers. Of the gene expression changes induced by TPL treatment, up-regulation of LRAP, CDH4, and SFRP1 and down-regulation of cystatin, TNNT 1, and L1-CAM were confirmed using Western blot analysis in all the cell lines examined. We found a strong anticancer activity of TPL and identified some potential target genes of this drug, raising hopes that TPL may become a useful therapy for endometrial and ovarian cancers.
雷公藤内酯醇（TPL）是中药雷公藤的一种生物活性成分，可诱导某些人类肿瘤细胞凋亡。然而，TPL 对妇科癌症细胞的作用尚未得到很好的描述。我们研究了 TPL 对子宫内膜和卵巢癌细胞系的细胞生长、细胞周期和凋亡的影响。此外，我们还研究了 TPL 处理后基因表达的全局变化。通过使用 20 个差异表达基因列表，对五种子宫内膜和卵巢癌细胞系进行了 Western blot 分析。所有细胞系均对 TPL 的生长抑制作用敏感。TPL 增加了细胞周期 S 期的比例并诱导了细胞凋亡。cDNA 微阵列分析表明，TPL 处理改变了细胞周期调节剂、凋亡相关因子和细胞增殖标志物的表达。通过 Western blot 分析，在所有检测的细胞系中均证实了 TPL 处理诱导的基因表达变化，包括 LRAP、CDH4 和 SFRP1 的上调以及cystatin、TNNT1 和 L1-CAM 的下调。我们发现 TPL 具有很强的抗癌活性，并确定了该药物的一些潜在靶基因，这增加了 TPL 可能成为子宫内膜和卵巢癌有用治疗方法的希望。
