The role of substance P/neurokinin 1 receptor in the pathogenesis of esophageal squamous cell carcinoma through constitutively active PI3K/Akt/NF-κB signal transduction pathways
| Autor: | Hossein Javid, Jahanbakhsh Asadi, Seyed Isaac Hashemy, Farnaz Zahedi Avval, Amir R Afshari |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Apoptosis Substance P Sulfuric Acid Esters Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Tachykinin receptor 1 Genetics medicine Humans Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Aprepitant Cell Proliferation Cell Cycle NF-kappa B General Medicine Receptors Neurokinin-1 Cell cycle G2 Phase Cell Cycle Checkpoints 030104 developmental biology chemistry Caspases 030220 oncology & carcinogenesis Cancer research NK1 receptor antagonist Disease Susceptibility Esophageal Squamous Cell Carcinoma Signal transduction Azo Compounds Proto-Oncogene Proteins c-akt Signal Transduction medicine.drug |
| Zdroj: | Molecular Biology Reports. 47:2253-2263 |
| ISSN: | 1573-4978 0301-4851 |
| Popis: | One of the most prevalent malignancies is esophageal squamous cell carcinoma (ESCC), which is associated with high morbidity and mortality. Substance P (SP), as one of the peptides released from sensory nerves, causes the enhancement of cellular excitability through the activation of the neurokinin-1 (NK1) receptor in several human tumor cells. Aprepitant, a specific, potent, and long-acting NK1 receptor antagonist, is considered as a novel agent to inhibit proliferation and induce apoptosis in malignant cells. Since the antitumor mechanism of aprepitant in ESCC is not completely understood, we conducted this study and found that aprepitant induced growth inhibition of KYSE-30 cells and arrested cells in the G2/M phase of the cell cycle. Aprepitant also caused apoptotic cell death and inhibited activation of the PI3K/Akt axis and its downstream effectors, including NF-κB in KYSE-30 cells. Besides, quantitative real-time (qRT)-PCR analysis showed a significant down-regulation of NF-κB target genes in KYSE-30 cells, indicating a probable NF-κB-dependent mechanism involved in aprepitant cytotoxicity. Thus, the present study recommends that SP/NK1R system might, therefore, be considered as an emerging and promising therapeutic strategy against ESCC. |
| Databáze: | OpenAIRE |
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