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Notch-4 silencing inhibits prostate cancer growth and EMT via the NF-κB pathway

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Abstract

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.

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Authors and Affiliations

  1. Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Jianwei Zhang, Yan Wang & Quanquan Xu

  2. Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

    Youlin Kuang

  3. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China

    Qinghua Ren

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  1. Jianwei Zhang
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Correspondence to Jianwei Zhang.

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Zhang, J., Kuang, Y., Wang, Y. et al. Notch-4 silencing inhibits prostate cancer growth and EMT via the NF-κB pathway. Apoptosis 22, 877–884 (2017). https://doi.org/10.1007/s10495-017-1368-0

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