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Triptolide (TPL) is a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii and possesses anti-tumor activity against a range of cancer cells. However, the effect of TPL on prostate cancer cells and its potential to overcome multidrug resistance (MDR) have not been explored. Therefore, in this study we used prostate cancer cell line DU145 as the experimental model and established DU145/ADM cell line resistant to adriamycin (ADM). Our results showed that TPL inhibited the proliferation and induced the cell cycle arrest and apoptosis of DU145 cells in a dose and time dependent manner. TPL decreased the levels of Cyclin D1 and anti-apoptotic protein Bcl-2, and increased the levels of pro-apoptotic proteins Fas and Bax. Furthermore, we found that TPL restored the sensitivity DU145/ADM cells to ADM in a dose dependent manner, and this was accompanied by the inhibition of MDR1 expression at both mRNA and protein levels. Taken together, these results provide strong evidence that TPL overcomes MDR in prostate cancer cells by downregulating MDR1 expression, and suggest that TPL is a promising agent for prostate cancer therapy, especially for chemoresistant prostate cancer.

Triptolide inhibits the multidrug resistance in prostate cancer cells via the downregulation of MDR1 expression