Journal Article

Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer

Hashemy, Seyed Isaac, Mozafari, Mahtab, Darban, Reza Assaran, Ebrahimi, Safieh

2022

Overview

Background Cervical cancer, an aggressive gynecological cancer, seriously threatens women’s health worldwide. It is recently reported that neuropeptide substance P (SP) regulates many tumor-associated processes through neurokinin-1 receptor (NK1R). Therefore, we used cervical cancer cell line (HeLa) to investigate the functional relevance of the SP/NK1R system in cervical cancer pathogenesis. Methods Cellular proliferation and cytotoxicity were analyzed by colorimetric MTT assay. Quantitative real-time PCR (qRT-PCR) was used to measure mRNA expression levels of desired genes. Cell cycle distribution and apoptosis were evaluated by flow cytometry. A wound-healing assay was employed to assess migration ability. Results We found that the truncated isoform of NK1R(NK1R-Tr) is the dominantly expressed form of the receptor in Hela cells . We also indicated that that SP increased HeLa cell proliferation while treatment with NK1R antagonist, aprepitant, inhibited HeLa cell viability in a dose and time-dependent manner. SP also alters the levels of cell cycle regulators (up-regulation of cyclin B1 along with downregulation of p21) and apoptosis-related genes (up-regulation of Bcl-2 along with downregulation of Bax) while aprepitant reversed these effects. Aprepitant also induced arrest within the G2 phase of the cell cycle and subsequent apoptosis. Furthermore, SP promoted the migrative phenotype of HeLa cells and increased MMP-2 and MMP-9 expression while aprepitant exposure significantly reversed these effects. Conclusion Collectively, our results indicate the importance of the SP / NK1R system in promoting both proliferative and migrative phenotypes of cervical cancer cells and suggest that aprepitant may be developed as a novel treatment for combating cervical cancer.

• Publisher: Springer Netherlands,Springer Nature B.V
• Subject: Animal Anatomy / Animal Biochemistry / antagonists / Apoptosis / Apoptosis - drug effects / Aprepitant - pharmacology / Bcl-2 protein / Biomedical and Life Sciences / Cell cycle / Cell Line, Tumor / Cell proliferation / Cell Proliferation - drug effects / Cell viability / Cervical cancer / Cervix / Colorimetry / Cyclin B1 / cyclins / Cytotoxicity / Female / Flow cytometry / G2 phase / Gelatinase A / Gelatinase B / Gene expression / Gene Expression - genetics / Gene Expression Regulation, Neoplastic - drug effects / Gene regulation / Gynecological cancer / HeLa Cells / Histology / human cell lines / Humans / interphase / Life Sciences / Matrix Metalloproteinase 2 / Matrix Metalloproteinase 9 / molecular biology / Morphology / neoplasm cells / Neurokinin / Neurokinin NK1 receptors / Neurokinin-1 Receptor Antagonists - pharmacology / Original Article / pathogenesis / phenotype / Phenotypes / quantitative polymerase chain reaction / Receptors, Neurokinin-1 - genetics / Receptors, Neurokinin-1 - metabolism / Signal Transduction - drug effects / Substance P / Substance P - metabolism / therapeutics / toxicity testing / Tumors / uterine cervical neoplasms / Uterine Cervical Neoplasms - genetics / Uterine Cervical Neoplasms - therapy / Wound healing