Malihe Golestaneh1, Mohsen Firoozrai2, Hossein Javid3, Seyed Isaac Hashemy4,5. 1. Student Research Committee, Clinical biochemistry Department, Medical Faculty, Shahrood Azad University, Shahrood, Iran. 2. Clinical biochemistry Department, Medical Faculty, Shahrood Azad University, Shahrood, Iran. 3. Medical Laboratory Sciences Department, Varastegan Institute for Medical Sciences, Mashhad, Iran. 4. Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. hashemyi@mums.ac.ir. 5. Department of Clinical Biochemistry Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. hashemyi@mums.ac.ir.
Abstract
BACKGROUND: The substance P (SP)/neurokinin-1 receptor (NK1R) system, a critical metastatic signaling pathway, can be targeted by substance P antagonists to prevent its cancer-progressive impacts. In the current study, we aimed to investigate the carcinogenic activity of the SP/NK1R system in human SW480 colorectal cancer cells and study the antagonistic impact of aprepitant (AP) by measuring MMP-2 and MMP-9 enzymatic activity. METHODS: Different concentrations of SP, alone or mixed by AP, were utilized to treat SW480 cells to investigate the cells' viability and metastasis by applying Resazurin and Gelatin Zymography methods, respectively. The cells' metastatic response was analyzed by measuring the MMP-2 and MMP-9 in transcriptional and translational levels. Finally, the Scratch assay was carried out to evaluate the cells' metastatic response following the SP/AP treatment. RESULTS: A significant metastatic activity was observed in SW480 cells following incubation with the increasing SP doses by detecting MMP-2/MMP-9 enzyme activity, genes overexpression, and enhanced cell migration. This is while the AP treatment meaningfully diminished all the SP-mediated metastatic effects (p-Value < 0.001). CONCLUSIONS: According to the results, the SP/NKR1 signaling pathway can be considered one of the main metastatic effectors in human colorectal cancer. Therefore, AP might be suggested to be used as the SP antagonist and an efficient anti-metastatic drug.
BACKGROUND: The substance P (SP)/neurokinin-1 receptor (NK1R) system, a critical metastatic signaling pathway, can be targeted by substance P antagonists to prevent its cancer-progressive impacts. In the current study, we aimed to investigate the carcinogenic activity of the SP/NK1R system in human SW480 colorectal cancer cells and study the antagonistic impact of aprepitant (AP) by measuring MMP-2 and MMP-9 enzymatic activity. METHODS: Different concentrations of SP, alone or mixed by AP, were utilized to treat SW480 cells to investigate the cells' viability and metastasis by applying Resazurin and Gelatin Zymography methods, respectively. The cells' metastatic response was analyzed by measuring the MMP-2 and MMP-9 in transcriptional and translational levels. Finally, the Scratch assay was carried out to evaluate the cells' metastatic response following the SP/AP treatment. RESULTS: A significant metastatic activity was observed in SW480 cells following incubation with the increasing SP doses by detecting MMP-2/MMP-9 enzyme activity, genes overexpression, and enhanced cell migration. This is while the AP treatment meaningfully diminished all the SP-mediated metastatic effects (p-Value < 0.001). CONCLUSIONS: According to the results, the SP/NKR1 signaling pathway can be considered one of the main metastatic effectors in human colorectal cancer. Therefore, AP might be suggested to be used as the SP antagonist and an efficient anti-metastatic drug.
Authors: M Kataoka; S Yamagata; H Takagi; A Thant; S Akiyama; K Iida; T Watanabe; S Saga; J Kishi; M Hamaguchi Journal: Int J Oncol Date: 1996-04 Impact factor: 5.650