Triptolide circumvents drug-resistant effect and enhances 5-fluorouracil antitumor effect on KB cells

被引:47
作者
Chen, Yuan-Wu [1 ,6 ]
Lin, Gu-Jiun [2 ,3 ]
Chuang, Yi-Ping [4 ]
Chia, Wei-Tso [1 ]
Hueng, Dueng-Yuan [7 ]
Lin, Chih-Kung [8 ]
Nieh, Shin [8 ]
Sytwu, Huey-Kang [1 ,2 ,4 ,5 ]
机构
[1] Tri Serv Gen Hosp, Natl Def Med Ctr, Grad Inst Med Sci, Taipei 114, Taiwan
[2] Tri Serv Gen Hosp, Natl Def Med Ctr, Grad Inst Life Sci, Taipei 114, Taiwan
[3] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Biol & Anat, Taipei 114, Taiwan
[4] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Microbiol & Immunol, Taipei 114, Taiwan
[5] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Med Res, Taipei 114, Taiwan
[6] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Oral & Maxillofacial Surg, Taipei 114, Taiwan
[7] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Neurol Surg, Taipei 114, Taiwan
[8] Tri Serv Gen Hosp, Natl Def Med Ctr, Dept Pathol, Taipei 114, Taiwan
关键词
5-fluorouracil; apoptosis; multi-drug resistance; synergistic effect; triptolide; FACTOR-KAPPA-B; TRIPTERYGIUM-WILFORDII; MULTIDRUG-RESISTANCE; MULTIPLE-MYELOMA; CARCINOMA-CELLS; DOWN-REGULATION; NITRIC-OXIDE; CANCER-CELLS; NECK-CANCER; PHASE-III;
D O I
10.1097/CAD.0b013e328337337c
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:502 / 513
页数:12
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