Maryam Momen Razmgah1, Atefeh Ghahremanloo1,2, Hossein Javid3, Abbas AlAlikhan2, Amir-R Afshari4, Seyed Isaac Hashemy5,6,7. 1. Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran. 4. Department of Physiology and Pharmacology, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran. 5. Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. hashemyi@mums.ac.ir. 6. Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. hashemyi@mums.ac.ir. 7. Department of Clinical Biochemistry Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. hashemyi@mums.ac.ir.
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.
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.
Authors: Witold Jeleniewicz; Marek Cybulski; Andrzej Nowakowski; Agnieszka Stenzel-Bembenek; Małgorzata Guz; Barbara Marzec-Kotarska; Jan Kotarski; Andrzej Stepulak Journal: Anticancer Res Date: 2019-04 Impact factor: 2.480