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The substance P/ neurokinin-1 receptor signaling pathway mediates metastasis in human colorectal SW480 cancer cells



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.


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.


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).


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.

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SIH was responsible for the conceptualization and supervision of the project. All authors contributed to the gathering of data. MG wrote the first draft of the manuscript, and SIH finalized and submitted the paper. All authors have read and approved the final format of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Seyed Isaac Hashemy MD-PhD.

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Golestaneh, M., Firoozrai, M., Javid, H. et al. The substance P/ neurokinin-1 receptor signaling pathway mediates metastasis in human colorectal SW480 cancer cells. Mol Biol Rep 49, 4893–4900 (2022).

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  • Substance P
  • Neurokinin 1 receptor
  • Metastasis
  • Aprepitant
  • Colorectal cancer