Substance P accelerates the progression of human esophageal squamous cell carcinoma via MMP-2, MMP-9, VEGF-A, and VEGFR1 overexpression.

Tachykinins such as Substance P (SP) are a group of neuropeptides that are involved in cancer development. Neurokinin-1 receptor (NK-1R) is the main tachykinin receptor mediating the effects of SP, which is overexpressed in human esophageal squamous cell carcinoma (ESCC) and other malignant tissues. However, the effects of SP/NK-1R system on the migration of esophageal cancer cells and angiogenesis is not clear yet. This study seeks to obtain data to address these research gaps. In order to assess the effects of the FDA-approved aprepitant drug, a commercially available NK-1R antagonist, on the viability of KYSE-30 ESCC cells, resazurin assay was performed. The influence of SP/NK-1R system on the migration potential of these cells was examined using scratch assay. The effects of this system on the expression levels of metastatic factors were also examined by RT-PCR and western blot analyses. The half-maximal inhibitory concentration (IC ₅₀ ) value for KYSE-30 cells treated with aprepitant found to be 29.88 μM. Treatment with SP significantly promoted KYSE-30 esophageal cancer cell migration, and aprepitant blocked this effect. In addition, SP significantly induced the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, vascular endothelial growth factor-A (VEGF-A), and VEGF receptor1 (VEGFR1) in the cells, whereas aprepitant inhibited the up-regulation effects caused by SP. SP plays important roles in the development of human esophageal squamous cell carcinoma by promoting cancer cell invasion and enhancing the expression of factors involved in cellular migration and angiogenesis, which can be blocked by the NK-1R antagonist, aprepitant.