Neoplasma. 2013;60(6):598-604. doi: 10.4149/neo_2013_077.
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.
雷公藤红素（TPL）是一种来源于中国草药雷公藤的二萜三环氧化合物，具有针对多种癌细胞的抗肿瘤活性。然而，TPL 对前列腺癌细胞的作用及其克服多药耐药性（MDR）的潜力尚未得到探索。因此，在这项研究中，我们使用前列腺癌细胞系 DU145 作为实验模型，并建立了对阿霉素（ADM）耐药的 DU145/ADM 细胞系。我们的结果表明，TPL 以剂量和时间依赖的方式抑制 DU145 细胞的增殖并诱导细胞周期停滞和细胞凋亡。TPL 降低了细胞周期蛋白 D1 和抗凋亡蛋白 Bcl-2 的水平，增加了促凋亡蛋白 Fas 和 Bax 的水平。此外，我们发现 TPL 以剂量依赖的方式恢复了 DU145/ADM 细胞对 ADM 的敏感性，同时抑制了 MDR1 在 mRNA 和蛋白水平的表达。总之，这些结果提供了强有力的证据，表明 TPL 通过下调 MDR1 的表达来克服前列腺癌细胞中的 MDR，这表明 TPL 是一种有前途的前列腺癌治疗药物，特别是用于治疗化疗耐药的前列腺癌。
