Department of Clinical Medicine, North Sichuan Medical College, Nanchong, China.
Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
Biomed Res Int. 2022 Oct 6;2022:9235837. doi: 10.1155/2022/9235837. eCollection 2022.
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 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 . 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.
去势抵抗性前列腺癌（CRPC）仍然难以治疗。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 患者无进展生存期（PFS）较差。这些蛋白的表达在恩杂鲁胺耐药 LNCaP 细胞（Enza-R）中也上调。此外，敲低 SOX8 抑制了 Enza-R 细胞的恶性生物学行为，并降低了 Notch 信号的激活。重要的是，敲低 SOX8 明显逆转了 Enza-R 细胞对恩杂鲁胺的耐药性，而 RO0429097（一种 γ-分泌酶抑制剂可使 Notch 信号失活）也产生了类似的效果。最后，我们发现 SOX8 敲低和/或 RO0429097 均抑制肿瘤生长和骨转移。总之，我们的研究表明 SOX8/Notch 信号参与了 CRPC，这些酶可能是开发治疗 CRPC 的新方法的潜在靶点。
