Triptolide circumvents drug-resistant effect and enhances 5-fluorouracil antitumor effect on KB cells
Triptolide circumvents drug-resistant effect and enhances 5-fluorouracil antitumor effect on KB cells
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DOI：
10.1097/cad.0b013e328337337c
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发表时间：
2010-06-01
影响因子：
2.3
通讯作者：
Sytwu, Huey-Kang
中科院分区：
文献类型：
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作者：
Chen, Yuan-Wu;Lin, Gu-Jiun;Sytwu, Huey-Kang
雷公藤内酯醇是从中药雷公藤中提取的一种二萜类三环氧化物，通过诱导KB癌细胞凋亡发挥抗肿瘤作用。在这项研究中，我们表明，雷公藤内酯醇具有对药物敏感的亲本KB细胞和多药耐药KB-7 D和KB-税务细胞，分别过表达多药耐药蛋白和MDR的抗癌作用。雷公藤内酯醇可降低KB-7 D和KB-tax细胞多药耐药蛋白的表达和MDR。它还通过激活caspase-3和减少Mcl-1和XIAP诱导这些多药耐药癌细胞的凋亡。雷公藤内酯醇不仅抑制肿瘤生长，而且在异种移植小鼠模型中诱导这些耐药癌细胞的凋亡。此外，我们还表明，雷公藤甲素联合5-氟尿嘧啶可能是一种替代的化疗增强策略。这些结果表明雷公藤内酯醇对多药耐药细胞的治疗价值，以及当与5-氟尿嘧啶联合使用时对增强癌症治疗的作用。抗癌药物21：502-513（C）2010年沃尔特斯·克鲁沃健康垂直栏Lippincott威廉姆斯&威尔金斯。
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. Anti-Cancer Drugs 21:502-513 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.