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Article Open Access

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

  • Authors:
    • Libin Ma
    • Kang Jiang
    • Peiwu Jiang
    • Han He
    • Kean Chen
    • Jia Shao
    • Gang Deng
  • View Affiliations / Copyright

    Affiliations: Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China, Department of Urology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China, Surgical Department Ⅰ, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang 310007, P.R. China
    Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 265-279
    |
    Published online on: May 8, 2020
       https://doi.org/10.3892/ijmm.2020.4597
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Abstract

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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Copy and paste a formatted citation
Spandidos Publications style
Ma L, Jiang K, Jiang P, He H, Chen K, Shao J and Deng G: Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer . Int J Mol Med 46: 265-279, 2020.
APA
Ma, L., Jiang, K., Jiang, P., He, H., Chen, K., Shao, J., & Deng, G. (2020). Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer . International Journal of Molecular Medicine, 46, 265-279. https://doi.org/10.3892/ijmm.2020.4597
MLA
Ma, L., Jiang, K., Jiang, P., He, H., Chen, K., Shao, J., Deng, G."Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer ". International Journal of Molecular Medicine 46.1 (2020): 265-279.
Chicago
Ma, L., Jiang, K., Jiang, P., He, H., Chen, K., Shao, J., Deng, G."Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer ". International Journal of Molecular Medicine 46, no. 1 (2020): 265-279. https://doi.org/10.3892/ijmm.2020.4597
Copy and paste a formatted citation
x
Spandidos Publications style
Ma L, Jiang K, Jiang P, He H, Chen K, Shao J and Deng G: Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer . Int J Mol Med 46: 265-279, 2020.
APA
Ma, L., Jiang, K., Jiang, P., He, H., Chen, K., Shao, J., & Deng, G. (2020). Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer . International Journal of Molecular Medicine, 46, 265-279. https://doi.org/10.3892/ijmm.2020.4597
MLA
Ma, L., Jiang, K., Jiang, P., He, H., Chen, K., Shao, J., Deng, G."Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer ". International Journal of Molecular Medicine 46.1 (2020): 265-279.
Chicago
Ma, L., Jiang, K., Jiang, P., He, H., Chen, K., Shao, J., Deng, G."Mechanism of Notch1‑saRNA‑1480 reversing androgen sensitivity in human metastatic castration‑resistant prostate cancer ". International Journal of Molecular Medicine 46, no. 1 (2020): 265-279. https://doi.org/10.3892/ijmm.2020.4597
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