Zhang Jianwei, Kuang Youlin, Wang Yan, Xu Quanquan, Ren Qinghua
Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.
Apoptosis. 2017 Jun;22(6):877-884. doi: 10.1007/s10495-017-1368-0.
Epithelial-mesenchymal transition (EMT) is implicated in the metastasis of human prostate cancer (PCa). Notch signaling has been established as a regulator of EMT. Notch-4 has emerged as a mammary proto-oncogene and a target in several cancers. However, the role and the mechanism of action of Notch-4 in PCa are still unclear. In the present study, we first observed a marked increase in Notch-4 expression in the PCa cell lines DU145, PC3 and LnCAP compared with the non-malignant prostate epithelial cell line RWPE1. Knocking down the expression of Notch-4 suppressed the viability and proliferation in the PCa cell lines DU145 and PC3. Also, further study showed that a decline in Notch-4 significantly promoted apoptosis in PC3 cells. Notch-4 silencing also resulted in decreased cell migration and invasion and affected the expression of EMT markers. We hypothesized that Notch-4 ablation suppresses the activity of NF-κB, so we used PMA to stimulate NF-κB p50 and p65 activation in PC3 cells. The results indicate that PMA treatment impaired the action of Notch-4 ablation in the biology of PC3 cells including cell growth, apoptosis, migration, invasion and EMT. The results of the present study show that RNAi targeting against Notch-4 expression suppresses PCa progression.
上皮-间质转化（EMT）与人类前列腺癌（PCa）的转移有关。Notch信号通路已被确认为EMT的调节因子。Notch-4已成为一种乳腺原癌基因和多种癌症的靶点。然而，Notch-4在PCa中的作用和作用机制仍不清楚。在本研究中，我们首先观察到与非恶性前列腺上皮细胞系RWPE1相比，PCa细胞系DU145、PC3和LnCAP中Notch-4的表达显著增加。敲低Notch-4的表达可抑制PCa细胞系DU145和PC3的活力和增殖。此外，进一步研究表明，Notch-4的下降显著促进了PC3细胞的凋亡。Notch-4沉默还导致细胞迁移和侵袭减少，并影响EMT标志物的表达。我们假设Notch-4缺失会抑制NF-κB的活性，因此我们使用佛波酯（PMA）刺激PC3细胞中NF-κB p50和p65的激活。结果表明，PMA处理削弱了Notch-4缺失对PC3细胞生物学行为（包括细胞生长、凋亡、迁移、侵袭和EMT）的作用。本研究结果表明，靶向Notch-4表达的RNA干扰可抑制PCa的进展。
