PDF(Pubmed)
Abstract：
Castration-resistant prostate cancer (CRPC) is still challenging to treat. Dissatisfaction with androgen signal-targeted therapy forces people to look for other treatment strategies. Therefore, this study is aimed at exploring the role of SOX8/Notch signaling in CRPC. The upregulation of SOX8, Notch4, and Hes5 indicated a poor progression-free survival (PFS) in CRPC patients. The expression of these proteins was also upregulated in enzalutamide-resistant LNCaP cells (Enza-R). Moreover, knocking down SOX8 inhibited malignant biological behaviors and decreased the activation of Notch signaling in Enza-R cells. Importantly, knocking down SOX8 obviously reversed the enzalutamide resistance in Enza-R cells, while RO0429097 (a γ secretase inhibitor inactivates Notch signaling) exerted similar effects. At last, we found that both SOX8 knockdown and/or RO0429097 suppressed tumor growth and bone metastasis in vivo. Altogether, our study indicated that the SOX8/Notch signaling is involved in CRPC and that these enzymes are possible targets to develop novel treatment for CRPC.
摘要：
去势抵抗性前列腺癌（CRPC）仍然具有挑战性。对雄激素信号靶向治疗的不满迫使人们寻找其他治疗策略。因此,本研究旨在探讨SOX8/Notch信号在CRPC中的作用。SOX8，Notch4和Hes5的上调表明CRPC患者的无进展生存期（PFS）较差。这些蛋白质的表达在恩杂鲁胺抗性LNCaP细胞(Enza-R)中也上调。此外，敲低SOX8可以抑制Enza-R细胞的恶性生物学行为，降低Notch信号的激活。重要的是,敲低SOX8可明显逆转Enza-R细胞对恩杂鲁胺的耐药性,而RO0429097(一种γ分泌酶抑制剂使Notch信号失活)发挥了类似的作用。最后,我们发现SOX8敲低和/或RO0429097在体内抑制肿瘤生长和骨转移。总之,我们的研究表明,SOX8/Notch信号与CRPC有关,这些酶可能是开发CRPC新治疗方法的靶点.
