PDF(Pubmed)
Abstract：
Sharply increased reactive oxygen species (ROS) are thought to induce oxidative stress, damage cell structure and cause cell death; however, its role in prostate cancer remains unclear. Enzalutamide is a widely used anti-prostate cancer drug that antagonizes androgen binding with its receptor. Further exploration of the mechanism and potential application strategies of enzalutamide is crucial for the treatment of prostate cancer. Here, we confirmed PEX10 can be induced by ROS activators while reduce ROS level in prostate cancer cells, which weakened the anti-tumor effect of ROS activators. The androgen receptor (AR) can promote the expression of PEX10 by acting as an enhancer in cooperation with FOXA1. The anti-tumor drug enzalutamide inhibits PEX10 by inhibiting the function of AR, and synergize with ROS activators ML210 or RSL3 to produce a stronger anti-tumor effect, thereby sensitizing cells to ROS activators. This study reveals a previously unrecognized function of enzalutamide and AR by regulating PEX10 and suggests a new strategy of enzalutamide application in prostate cancer treatment.
摘要：
急剧增加的活性氧（ROS）被认为是诱导氧化应激，破坏细胞结构并导致细胞死亡；然而，其在前列腺癌中的作用尚不清楚。恩扎鲁胺是一种广泛使用的抗前列腺癌药物，可拮抗雄激素与其受体的结合。进一步探索恩杂鲁胺的作用机制和潜在应用策略对前列腺癌的治疗至关重要。这里,我们证实PEX10可以被ROS激活剂诱导，同时降低前列腺癌细胞中的ROS水平，从而削弱了ROS激活剂的抗肿瘤作用。雄激素受体(AR)可通过与FOXA1配合作为增强剂促进PEX10的表达。抗肿瘤药物恩杂鲁胺通过抑制AR的功能来抑制PEX10，并与ROS激活剂ML210或RSL3协同产生更强的抗肿瘤作用，从而使细胞对ROS激活剂敏感。这项研究揭示了恩杂鲁胺和AR通过调节PEX10的先前未被识别的功能，并提出了恩杂鲁胺在前列腺癌治疗中应用的新策略。
