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首页> 美国卫生研究院文献>Oncotarget >Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms
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Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms

机译：中药雷公藤通过多种机制克服前列腺癌的化学耐药性

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A leading cause of cancer chemotherapy failure is chemoresistance, which often involves multiple mechanisms. Chinese medicines (CM) usually contain multiple components which could potentially target many mechanisms simultaneously and may offer an advantage over single compounds that target one mechanism at a time. The purpose of this study was to investigate the chemosensitizing effect (CE) of a specific CM, Tripterygium wilfordii (TW), on prostate cancer cells resistant to docetaxel (Dtx) and identify the potential mechanisms. The CE of TW (in combination with Dtx) was evaluated in two Dtx resistant prostate cancer cell lines (PC3-TxR and DU145-TxR) and the efficacy of the combination for resistant PC3-TxR tumor was investigated using a xenograft mouse model. For mechanistic study, the inhibitory effect of TW on P-glycoprotein activity was assessed. In addition, novel gene targets of TW were identified using DNA microarray and quantitative PCR. Results showed that TW induced a CE of 8 and >38 folds in PC3-TxR and DU145-TxR cells, respectively with Dtx IC50 reversed back to that of the sensitive parent cells. An optimum dose of TW+Dtx significantly retarded tumor growth in mice compared to TW or Dtx alone. TW inhibited P-glycoprotein activity and induced a significant gene expression changes in genes related to angiogenesis, cell cycle regulation and differentiation. Our in vitro and in vivo studies demonstrate that TW in combination with Dtx was able to overcome the chemoresistance and suppress resistant prostate tumor growth via multi-mechanisms.
机译：癌症化疗失败的主要原因是化学抗性，它通常涉及多种机制。中药（CM）通常包含多种成分，这些成分可能同时靶向多种机制，并且可能比一次靶向一种机制的单一化合物更具优势。这项研究的目的是调查特定的CM雷公藤（TW）对多西紫杉醇（Dtx）耐药的前列腺癌细胞的化学增敏作用（CE），并确定其潜在机制。在两种抗Dtx的前列腺癌细胞系（PC3-TxR和DU145-TxR）中评估了TW（与Dtx组合）的CE，并使用异种移植小鼠模型研究了该组合对PC3-TxR耐药性的功效。为了进行机理研究，评估了TW对P-糖蛋白活性的抑制作用。另外，使用DNA微阵列和定量PCR鉴定了TW的新基因靶标。结果显示，TW分别在PC3-TxR和DU145-TxR细胞中诱导了8倍和38倍的CE，而Dtx IC50却又回到了敏感母细胞的CE50。与单独使用TW或Dtx相比，最佳剂量的TW + Dtx显着延迟了小鼠的肿瘤生长。 TW抑制P-糖蛋白活性，并在与血管生成，细胞周期调控和分化有关的基因中诱导显着的基因表达变化。我们的体外和体内研究表明，TW与Dtx结合能够通过多种机制克服化学耐药性并抑制耐药性前列腺肿瘤的生长。

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