Triptolide (TPL) is a traditional Chinese medicine that possesses anti-multidrug resistance (MDR) properties against various cancers, including oral cancer. However, the functional roles of TPL in oral cancer cells and its potential ability to overcome MDR have not fully evaluated. Therefore, in this study we used oral cancer cell line SAS to establish Taxol-resistant cell line SAS/Taxol and investigated the effects of TPL on MDR, proliferation, and apoptosis of SAS/Taxol cells. We first demonstrated that TPL overcame MDR in SAS/Taxol cells. In addition, TPL induced prominent proliferation inhibition, cell cycle arrest, and apoptosis of SAS/Taxol cells. Furthermore, the pro-apoptotic effect of TPL on SAS/Taxol cells was dependent on intrinsic and extrinsic apoptotic pathways involved in the activation of caspases. Consistently, TPL successfully hampered oral tumor growth by inducing cell apoptosis in a xenograft mouse model. Overall, these results indicated that TPL circumvented MDR of SAS/Taxol cells by inhibition of proliferation and induction of apoptosis which was partly mediated by the intrinsic and extrinsic apoptotic pathways, suggesting the potential therapeutic value of TPL on Taxol-resistant human oral cancer.
Keywords: Triptolide; apoptosis; multidrug-resistance; oral cancer; proliferation.
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