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The effect of substance P and its specific antagonist (aprepitant) on the expression of MMP-2, MMP-9, VEGF, and VEGFR in ovarian cancer cells

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Abstract

Background

Substance P (SP) has a crucial role in cancer initiation and progression via binding to its specific receptor (NK1R). Various evidence confirmed the overexpression of NK1R and SP in the tissue of multiple cancers, including ovarian cancer. Despite numerous studies, the mechanism of the SP/NK1R system on migration and angiogenesis of ovarian cancer cells has not yet been deciphered. In this study, considering the critical factors in cell migration (MMP-2, MMP-9) and angiogenesis (VEGF, VEGFR), we investigated the possible mechanism of this system in inducing migration and angiogenesis of ovarian cancer cells.

Methods and Results

First, the resazurin assay was conducted to evaluate the cytotoxic effect of aprepitant (NK1R antagonist) on the viability of A2780 ovarian cancer cells. After that, the impact of this system and aprepitant on the mRNA expression of the factors mentioned above were studied using RT-PCR. Besides, the scratch assay was performed to confirm the effect of the SP/NK-1R system and aprepitant on cell migration. Our results implied that this system induced cell migration and angiogenesis by increasing the mRNA expression of MMP-2, MMP-9, VEGF, and VEGFR. The obtained results from the scratch assay also confirmed the positive effect of this system on cell migration. Meanwhile, the blocking of NK1R by aprepitant suppresses the SP effects on cell migration and angiogenesis.

Conclusions

Overall, the SP/NK1R system plays a vital role in ovarian cancer progression, and the inhibition of NK1Rusing aprepitant could inhibit the spread of ovarian cancer cells through metastasis and angiogenesis.

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Acknowledgements

This paper is taken from the dissertation of Maryam Momen Razmgah (MD thesis), and the project is financially supported by the Research Council of Mashhad University of Medical Sciences (Grant number: 981453).

Funding

This research was funded by the Research Council of Mashhad University of Medical Sciences (Grant number: 981453).

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Authors and Affiliations

  1. Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Maryam Momen Razmgah & Atefeh Ghahremanloo

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

    Atefeh Ghahremanloo, Abbas AlAlikhan & Seyed Isaac Hashemy

  3. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran

    Hossein Javid

  4. Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran

    Amir-R Afshari

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

    Seyed Isaac Hashemy

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

    Seyed Isaac Hashemy

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  1. Maryam Momen Razmgah
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  5. Amir-R Afshari
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All authors contributed to the design and direction of the project. M.M.R, A.G, H.J, and A.A participated in data collection, analysis, and writing the article. All authors read and approved the final manuscript.

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Correspondence to Seyed Isaac Hashemy.

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Momen Razmgah, M., Ghahremanloo, A., Javid, H. et al. The effect of substance P and its specific antagonist (aprepitant) on the expression of MMP-2, MMP-9, VEGF, and VEGFR in ovarian cancer cells. Mol Biol Rep 49, 9307–9314 (2022). https://doi.org/10.1007/s11033-022-07771-w

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