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Updated: Feb 3, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

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Alterations of tumor microenvironment by nitric oxide impedes castration-resistant prostate cancer growth

Himanshu Arora1,2, Kush Panara3, Manish Kuchakulla3

  • 1Department of Urology, Miller School of Medicine, University of Miami, Miami, FL 33136; hxa287@miami.edu andrew.schally@va.gov ramasamy@miami.edu.

Proceedings of the National Academy of Sciences of the United States of America
|October 17, 2018
PubMed

Insights

Nitric oxide (NO) therapy shows promise for advanced prostate cancer. S-nitrosoglutathione (GSNO) reduced castration-resistant prostate cancer (CRPC) tumor growth by modulating the tumor microenvironment and immune cells.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Nitric oxide (NO) synthases are explored for advanced prostate cancer therapy.
  • The role of NO in castration-resistant prostate cancer (CRPC) is debated due to conflicting anti-inflammatory and pro-oxidative effects.
  • Understanding NO's impact on the CRPC tumor microenvironment (TME) is crucial.

Purpose of the Study:

  • To investigate the hypothesis that increased NO can suppress CRPC growth via TME modulation.
  • To evaluate the therapeutic potential of NO donors in CRPC models.

Main Methods:

  • Utilized a murine model of CRPC.
  • Administered S-nitrosoglutathione (GSNO), an NO donor, to assess tumor burden.
  • Analyzed changes in tumor-associated macrophages (M2), pERK expression, IL-34, G-CSF, and M-CSF.
  • Validated findings in secondary xenograft models.

Main Results:

  • GSNO significantly decreased CRPC tumor burden in mice.
  • GSNO inhibited M2 macrophages and pERK expression, suggesting NO influences tumor-associated macrophage activity.
  • GSNO suppressed IL-34, indicating reduced tumor-associated macrophage differentiation.
  • Reduced G-CSF and M-CSF levels were observed in GSNO-treated CRPC tumors.
  • NO's inhibitory effect on CRPC was durable and reproducible.

Conclusions:

  • NO plays a significant role in inhibiting CRPC progression through TME regulation.
  • GSNO demonstrates therapeutic potential for CRPC by targeting the tumor microenvironment.
  • These findings support the development of novel NO-based therapies for CRPC.
Keywords:
CRPCimmunotherapynitric oxidetumor microenvironmenttumor-associated macrophages

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