Triptolide exerts antitumor effect, circumvents drug-resistant effect, and enhances 5-fluorouracil anti-tumor effect on oral cancer cells and KB cells

• Main Authors: Yuan-Wu Chen, 陳元武
• Other Authors: Huey-Kang Sytwu
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/78674812586576768267

博士 === 國防醫學院 === 醫學科學研究所 === 98 === Abstract The aim of this study was to test whether Triptolide possess inhibitory effect of oral cancer. Triptolide (TPL), a diterpenoid triepoxide purified from the Chinese herb Tripterygium wilfordii Hook F. Recently, TPL has been reported to exhibit potential on anti-tumor proliferation in many cancer cells. However, the treatment effect of TPL on oral cancer or cancer cell lines are still undetermined. Herein we reported that TPL induced prominent growth inhibition and apoptosis in three oral cancer cell lines (KB, SCC25 and OEC-M1 cell line). First, at nM range TPL induced apoptosis which was also confirmed by annexin V staining to detect externalization of phosphatidylserine on the cell membrane. TPL also induced caspase 8, caspase 9 and caspase 3 activaton in these cancer cells. In vivo, TPL had anticancer effect in tumor bearing model via inducing cancer cells apoptosis by Tunel assay. Second, we also demonstrate that triptolide possesses an anti-cancer effect on drug-sensitive parental KB cells and multidrug-resistant KB-7D and KB-tax cells that overexpress MRP and MDR, respectively. Our data revealed that triptolide decreases the expression of MRP 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. Third, we also reveal that triptolide combined with 5-fluorouracil could be an alternative strategy for chemotherapy enhancement. These results may lead the usage of TPL on chemotherapy and chemoprevention in oral cancer, and when combined with 5-fluorouracil for the enhancement of cancer therapy in multidrug-resistant cells.