PRECLINICAL REPORTSTriptolide circumvents drug-resistant effect and enhances 5-fluorouracil antitumor effect on KB cellsChen, Yuan-Wua f; Lin, Gu-Jiunb c; Chuang, Yi-Pingd; Chia, Wei-Tsoa; Hueng, Dueng-Yuang; Lin, Chih-Kungh; Nieh, Shinh; Sytwu, Huey-Kanga b d eAuthor Information aGraduate Institute of Medical Sciences bGraduate Institute of Life Sciences Departments of cBiology and Anatomy dMicrobiology and Immunology eMedical Research, Tri-Service General Hospital, National Defense Medical Center Departments of fOral and Maxillofacial Surgery gNeurological Surgery hPathology, Tri-Service General Hospital, National Defense Medical Center, Taiwan, Republic of China Correspondence to Professor Huey-Kang Sytwu, Graduate Institute of Medical Sciences, National Defense Medical Center, No.161, Section 6, Min-Chuan East Road, Neihu 114, Taipei 114, Taiwan, Republic of China Tel: +886 2 87923100 x18540; fax: +886 2 87921774; e-mail: firstname.lastname@example.org Received 10 August 2009 Revised form accepted 5 January 2010 Anti-Cancer Drugs: June 2010 - Volume 21 - Issue 5 - p 502-513 doi: 10.1097/CAD.0b013e328337337c Buy Metrics Abstract 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. © 2010 Lippincott Williams & Wilkins, Inc.