Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer.

Published on Jul 1, 2020in International Journal of Molecular Medicine3.098
· DOI :10.3892/IJMM.2020.4597
Libin Ma3
Estimated H-index: 3
(ZJU: Zhejiang University),
Kang Jiang1
Estimated H-index: 1
(ZJU: Zhejiang University)
+ 4 AuthorsGang Deng1
Estimated H-index: 1
(ZJU: Zhejiang University)
The aim of the present study was to explore the mechanism by which Notch1‑small activating (sa)RNA restored androgen sensitivity in human metastatic castration‑resistant prostate cancer (CRPC). After transfection of Notch1‑saRNA‑1480 in PC3 cells, the expression of Notch1 and androgen receptor (AR) was investigated by reverse transcription quantitative PCR (RT‑qPCR) and western blotting. Furthermore, the protein expression level of vascular endothelial growth factor (VEGF) was measured. Then, flow cytometry was used to analyze the cell cycle and apoptosis after transfection. Moreover, the migration and invasion ability of PC3 cells were assessed by transwell assays. Then, angiogenesis experiments were conducted to analyze the abilities of PC3 cells to form blood vessels. Furthermore, in vivo experiments detected the antitumor activity of Notch1‑saRNA‑1480. The mRNA and protein expression levels of Notch1 were significantly increased after transfection, while the expression levels of AR and VEGF were decreased. After transfection, the cell cycle was arrested at the G0/G1 checkpoint. Notch1‑saRNA‑1480 significantly increased the proportion of apoptotic cells after transfection. In addition, transwell assay results showed that PC3 cell migration and invasion were inhibited. The total vessel length was significantly decreased based on angiogenesis experiments, which indicated that PC3 cell angiogenesis was inhibited. In vivo experiments showed that Notch1‑saRNA‑1480 could inhibit tumor growth and volume. The protein expression of Notch1, AR, VEGF receptor 2 (VEGFR2) and VEGF in tumor tissues was consistent with in vitro levels. Notch1‑saRNA‑1480 could significantly inhibit the proliferation of PC3 cells in vitro and the growth of tumors in vivo, which is associated with the inhibition of the AR and VEGF pathways.
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