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The In Vitro Pro-inflammatory Functions of the SP/NK1R System in Prostate Cancer: a Focus on Nuclear Factor-Kappa B (NF-κB) and Its Pro-inflammatory Target Genes

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Abstract

Prostate cancer is one of the main global health threats for men which is in close association with chronic inflammation. Neuropeptide substance P (SP), acting through neurokinin receptor (NK‐1R), induces various pro-inflammatory responses which are strongly involved in the pathogenesis of several diseases as well as cancer. Therefore, we aimed to investigate the pro-inflammatory functions of the SP/NK1R complex in prostate cancer and the therapeutic effects of its inhibition by NK‐1R antagonist, aprepitant, in vitro. MTT assay was conducted for the cytotoxicity assessment of aprepitant in prostate cancer cells. The protein expression levels were evaluated by Western blot assay. Quantitative real-time PCR (qRT-PCR) was applied to measure mRNA expression levels of pro-inflammatory cytokines. Concurrently, the protein concentrations of pro-inflammatory cytokines were also analyzed by enzyme-linked immunosorbent assay. We observed that SP increased the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), while treatment with aprepitant reduced the effects of SP. We also indicated that SP increased the protein levels of nuclear factor-kappa B (NF-κB), as the main regulator of inflammatory processes, and also an NF-κB target gene, cyclooxygenase 2 (COX-2) in prostate cancer cells, while treatment with aprepitant reversed these effects. Taken together, our findings highlight the importance of the SP/NK1R system in the modulation of pro-inflammatory responses in prostate cancer cells and suggest that aprepitant may be developed as a novel anti-inflammatory agent for the management of cancer-associated inflammation.

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The data are available from the corresponding author on reasonable request.

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Funding

This work was financially supported by the Research Council, Mashhad University of Medical Sciences (grant number: 4001500).

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Author notes

  1. Safieh Ebrahimi and Bahareh Erfani have contributed equally to this study.

Authors and Affiliations

  1. Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Safieh Ebrahimi, Bahareh Erfani, Abbas Alalikhan, BaratAli Mashkani & Seyed Isaac Hashemy

  2. Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran

    Safieh Ebrahimi, Bahareh Erfani & Abbas Alalikhan

  3. Kidney Transplantation Complication Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamidreza Ghorbani

  4. Department of Pathology, Mashhad University of Medical Sciences, Mashhad, Iran

    Mahdi Farzadnia

  5. Department of Physiology and Pharmacology, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

    Amir R. Afshari

  6. Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed Isaac Hashemy

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Contributions

Conceptualization: SE and SIH. Methodology: SE and BE. Formal analysis: SE, BE, and AA. Writing—original draft preparation: SE, BE. Writing—review and editing: all authors. Supervision: SIH. Project administration: SIH, BAM, ARA, MF, HRG. Funding acquisition: SIH. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Seyed Isaac Hashemy.

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Ebrahimi, S., Erfani, B., Alalikhan, A. et al. The In Vitro Pro-inflammatory Functions of the SP/NK1R System in Prostate Cancer: a Focus on Nuclear Factor-Kappa B (NF-κB) and Its Pro-inflammatory Target Genes. Appl Biochem Biotechnol 195, 7796–7807 (2023). https://doi.org/10.1007/s12010-023-04495-w

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