Graduate Institute of Medical Sciences, National Defense Medical Center, Taiwan, Republic of China.
Anticancer Drugs. 2010 Jun;21(5):502-13. doi: 10.1097/CAD.0b013e328337337c.
Triptolide, a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, exerts an antitumor effect in KB cancer cells through the induction of apoptosis. In this study, we show that triptolide possesses an anticancer effect on drug-sensitive parental KB cells and multidrug-resistant KB-7D and KB-tax cells that overexpress multidrug resistance protein and MDR, respectively. Our data revealed that triptolide decreases the expression of multidrug resistance protein and MDR in both KB-7D and KB-tax cells. It also induces apoptosis in these multidrug-resistant cancer cells by activating caspase-3, and decreasing Mcl-1 and XIAP. Triptolide not only inhibits tumor growth but also induces apoptosis of these drug-resistant cancer cells in xenograft mouse models. Moreover, we also show that triptolide combined with 5-fluorouracil could be an alternative strategy for chemotherapy enhancement. These results indicate the therapeutic value of triptolide on multidrug-resistant cells, and when combined with 5-fluorouracil for the enhancement of cancer therapy.
雷公藤红素是从中国草药雷公藤中提取的二萜三环氧化合物，通过诱导细胞凋亡发挥抗肿瘤作用。在本研究中，我们表明雷公藤红素对敏感亲本 KB 细胞以及分别过表达多药耐药蛋白和 MDR 的多药耐药 KB-7D 和 KB-tax 细胞具有抗癌作用。我们的数据显示，雷公藤红素降低了 KB-7D 和 KB-tax 细胞中多药耐药蛋白和 MDR 的表达。它还通过激活 caspase-3 并降低 Mcl-1 和 XIAP 诱导这些多药耐药癌细胞凋亡。雷公藤红素不仅抑制肿瘤生长，还能诱导这些耐药癌细胞在异种移植小鼠模型中的凋亡。此外，我们还表明，雷公藤红素与 5-氟尿嘧啶联合应用可能是化疗增强的一种替代策略。这些结果表明雷公藤红素对多药耐药细胞具有治疗价值，并且与 5-氟尿嘧啶联合应用可增强癌症治疗效果。
