The SP/NKR1 induction as the suppressible metastasis inducer by aprepitant antagonistic impact on human colorectal SW480 cancer cells
The SP/NKR1 induction as the suppressible metastasis inducer by aprepitant antagonistic impact on human colorectal SW480 cancer cells
Malihe Golestaneh,1,*Mohsen Firoozrai,2Seyed Isaac Hashemy,3Hossein Javid,4
1. Student Research Committee, Clinical biochemistry Department, Medical faculty, Shahrood Azad University 2. Professor, Clinical biochemistry Department, Medical faculty, Shahrood Azad University 3. Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad 4. Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Introduction: Substance P (SP)/ neurokinin-1receptor (NK1R) as the key metastasis 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 SP/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 and mixed by AP were exposed to the SW480 cell line 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 both transcription and translation levels. Finally, the Scratch Assay was carried out to evaluate the cells' metastatic response following SP/AP treatment doses.
Results: A significant metastatic activity was observed in SW480 cells following the increasing SP treatment doses by detecting MMP-2/MMP-9 enzyme activity, genes overexpression, and enhanced cell migration. This is while the AP treatment doses meaningfully diminished all the SP-mediated metastatic impacts (p-Value<0.001).
Conclusion: According to the results, the SP/NKR1 signaling pathway has the potential to be considered as one of the main metastatic effectors in human colorectal cancer. Moreover, the AP compound is suggested to be used as the SP antagonist and an efficient anti-metastatic compound.