Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
July-2023 Volume 50 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2023 Volume 50 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML

  • Supplementary Files
    • Supplementary_Data.pdf
Article Open Access

Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor

  • Authors:
    • Yang Zheng
    • Meixiang Sang
    • Fei Liu
    • Lina Gu
    • Juan Li
    • Yunyan Wu
    • Baoen Shan
  • View Affiliations / Copyright

    Affiliations: Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China
    Copyright: © Zheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 131
    |
    Published online on: May 9, 2023
       https://doi.org/10.3892/or.2023.8568
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Increasing evidence showed that the substance P (SP)/neurokinin‑1 receptor (NK1R) complex is involved in the development of several cancers. However, little is known about the mechanisms by which SP/NK1R complex plays a role in esophageal squamous cell carcinoma (ESCC) progression. RT‑qPCR, CCK‑8, Transwell, western blotting, immunohistochemical, immunofluorescence, ELISA and analysis of apoptosis were employed in the present study. It was aimed to investigate the function and therapeutic potential of the SP/tr‑NK1R system in human ESCC progression. The results revealed that both SP and tr‑NK1R were highly expressed in ESCC cell lines and specimens. In ESCC tissues, SP was mainly derived from ESCC cells and M2 macrophages. The NK1R antagonist aprepitant inhibited the SP‑induced proliferation of human ESCC cell lines. Aprepitant inhibited cell migration and invasion and induced apoptosis of ESCC cells by downregulating the PI3K/AKT/mTOR signaling pathways. Animal experiments revealed that aprepitant inhibited tumor progression of ESCC in xenograft mice. In conclusion, high expression of SP plus tr‑NK1R indicated poor prognosis in ESCC, suggesting that aprepitant has a potential application in ESCC. To the best of our knowledge, high SP and tr‑NK1R expression in ESCC cell lines was reported for the first time in the present study. These findings provided evidence for a novel therapeutic strategy for patients with ESCC.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Siegel RL, Miller KD, Fuchs HE and Jemal A: Cancer statistics, 2022. CA Cancer J Clin. 72:7–33. 2022. View Article : Google Scholar : PubMed/NCBI

2 

Abnet CC, Arnold M and Wei WQ: Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 154:360–373. 2018. View Article : Google Scholar : PubMed/NCBI

3 

Coveñas R and Muñoz M: Cancer progression and substance P. Histol Histopathol. 29:881–890. 2014.PubMed/NCBI

4 

González-Moles MÁ, Ramos-García P and Esteban F: Significance of the overexpression of substance P and its receptor NK-1R in head and neck carcinogenesis: A systematic review and meta-analysis. Cancers (Basel). 13:13492021. View Article : Google Scholar : PubMed/NCBI

5 

Patel HJ, Ramkissoon SH, Patel PS and Rameshwar P: Transformation of breast cells by truncated neurokinin-1 receptor is secondary to activation by preprotachykinin-A peptides. Proc Natl Acad Sci USA. 102:17436–17441. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Gillespie E, Leeman SE, Watts LA, Coukos JA, O'Brien MJ, Cerda SR, Farraye FA, Stucchi AF and Becker JM: Truncated neurokinin-1 receptor is increased in colonic epithelial cells from patients with colitis-associated cancer. Proc Natl Acad Sci USA. 108:17420–17425. 2011. View Article : Google Scholar : PubMed/NCBI

7 

Ramkissoon SH, Patel PS, Taborga M and Rameshwar P: Nuclear factor-kappaB is central to the expression of truncated neurokinin-1 receptor in breast cancer: Implication for breast cancer cell quiescence within bone marrow stroma. Cancer Res. 67:1653–1659. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Berger M, Neth O, Ilmer M, Garnier A, Salinas-Martín MV, de Agustín Asencio JC, von Schweinitz D, Kappler R and Muñoz M: Hepatoblastoma cells express truncated neurokinin-1 receptor and can be growth inhibited by aprepitant in vitro and in vivo. J Hepatol. 60:985–994. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Deng XT, Tang SM, Wu PY, Li QP, Ge XX, Xu BM, Wang HS and Miao L: SP/NK-1R promotes gallbladder cancer cell proliferation and migration. J Cell Mol Med. 23:7961–7973. 2019. View Article : Google Scholar : PubMed/NCBI

10 

Inoue T, Kimura M, Uchida J, Nishino K, Kumagai T, Taniguchi J and Imamura F: Aprepitant for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy. Int J Clin Oncol. 22:600–604. 2017. View Article : Google Scholar : PubMed/NCBI

11 

Yahata H, Kobayashi H, Sonoda K, Shimokawa M, Ohgami T, Saito T, Ogawa S, Sakai K, Ichinoe A, Ueoka Y, et al: Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: A multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin. Int J Clin Oncol. 21:491–497. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Muñoz M and Coveñas R: Neurokinin-1 receptor antagonists as antitumor drugs in gastrointestinal cancer: A new approach. Saudi J Gastroenterol. 22:260–268. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Douglas SD and Leeman SE: Neurokinin-1 receptor: Functional significance in the immune system in reference to selected infections and inflammation. Ann N Y Acad Sci. 1217:83–95. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Ge C, Huang H, Huang F, Yang T, Zhang T, Wu H, Zhou H, Chen Q, Shi Y, Sun Y, et al: Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload. Proc Natl Acad Sci USA. 116:19635–19645. 2019. View Article : Google Scholar : PubMed/NCBI

16 

Chanmee T, Ontong P, Konno K and Itano N: Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel). 6:1670–1690. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Zhou Y, Zhao L, Xiong T, Chen X, Zhang Y, Yu M, Yang J and Yao Z: Roles of full-length and truncated neurokinin-1 receptors on tumor progression and distant metastasis in human breast cancer. Breast Cancer Res Treat. 140:49–61. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Lewis KM, Harford-Wright E, Vink R and Ghabriel MN: NK1 receptor antagonists and dexamethasone as anticancer agents in vitro and in a model of brain tumours secondary to breast cancer. Anticancer Drugs. 24:344–354. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Javid H, Mohammadi F, Zahiri E and Hashemy SI: The emerging role of substance P/neurokinin-1 receptor signaling pathways in growth and development of tumor cells. J Physiol Biochem. 75:415–421. 2019. View Article : Google Scholar : PubMed/NCBI

20 

Garcia-Recio S, Fuster G, Fernandez-Nogueira P, Pastor-Arroyo EM, Park SY, Mayordomo C, Ametller E, Mancino M, Gonzalez-Farre X, Russnes HG, et al: Substance P autocrine signaling contributes to persistent HER2 activation that drives malignant progression and drug resistance in breast cancer. Cancer Res. 73:6424–6434. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Ma J, Yuan S, Cheng J, Kang S, Zhao W and Zhang J: Substance P promotes the progression of endometrial adenocarcinoma. Int J Gynecol Cancer. 26:845–850. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Esteban F, Muñoz M, González-Moles MA and Rosso M: A role for substance P in cancer promotion and progression: A mechanism to counteract intracellular death signals following oncogene activation or DNA damage. Cancer Metastasis Rev. 25:137–145. 2006. View Article : Google Scholar : PubMed/NCBI

23 

Mohammadi F, Javid H, Afshari AR, Mashkani B and Hashemy SI: Substance P accelerates the progression of human esophageal squamous cell carcinoma via MMP-2, MMP-9, VEGF-A, and VEGFR1 overexpression. Mol Biol Rep. 47:4263–4272. 2020. View Article : Google Scholar : PubMed/NCBI

24 

Mayordomo C, García-Recio S, Ametller E, Fernández-Nogueira P, Pastor-Arroyo EM, Vinyals L, Casas I, Gascón P and Almendro V: Targeting of substance P induces cancer cell death and decreases the steady state of EGFR and Her2. J Cell Physiol. 227:1358–1366. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Cui Y, Zhang S, Hu X and Gao F: Tumor-associated fibroblasts derived exosomes induce the proliferation and cisplatin resistance in esophageal squamous cell carcinoma cells through RIG-I/IFN-β signaling. Bioengineered. 13:12462–12474. 2022. View Article : Google Scholar : PubMed/NCBI

26 

Ho WZ, Lai JP, Zhu XH, Uvaydova M and Douglas SD: Human monocytes and macrophages express substance P and neurokinin-1 receptor. J Immunol. 159:5654–5660. 1997. View Article : Google Scholar : PubMed/NCBI

27 

Dupuis LL, Lingertat-Walsh K and Walker SE: Stability of an extemporaneous oral liquid aprepitant formulation. Support Care Cancer. 17:701–706. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Munoz M, Covenas R, Esteban F and Redondo M: The substance P/NK-1 receptor system: NK-1 receptor antagonists as anti-cancer drugs. J Biosci. 40:441–463. 2015. View Article : Google Scholar : PubMed/NCBI

29 

Rapoport BL, Jordan K, Boice JA, Taylor A, Brown C, Hardwick JS, Carides A, Webb T and Schmoll HJ: Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: A randomized, double-blind study. Support Care Cancer. 18:423–431. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Muñoz M and Rosso M: The NK-1 receptor antagonist aprepitant as a broad spectrum antitumor drug. Invest New Drugs. 28:187–193. 2010. View Article : Google Scholar : PubMed/NCBI

31 

Palma C, Bigioni M, Irrissuto C, Nardelli F, Maggi CA and Manzini S: Anti-tumour activity of tachykinin NK1 receptor antagonists on human glioma U373 MG xenograft. Br J Cancer. 82:480–487. 2000. View Article : Google Scholar : PubMed/NCBI

32 

Bigioni M, Benzo A, Irrissuto C, Maggi CA and Goso C: Role of NK-1 and NK-2 tachykinin receptor antagonism on the growth of human breast carcinoma cell line MDA-MB-231. Anticancer Drugs. 16:1083–1089. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zheng Y, Sang M, Liu F, Gu L, Li J, Wu Y and Shan B: Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor. Oncol Rep 50: 131, 2023.
APA
Zheng, Y., Sang, M., Liu, F., Gu, L., Li, J., Wu, Y., & Shan, B. (2023). Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor. Oncology Reports, 50, 131. https://doi.org/10.3892/or.2023.8568
MLA
Zheng, Y., Sang, M., Liu, F., Gu, L., Li, J., Wu, Y., Shan, B."Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor". Oncology Reports 50.1 (2023): 131.
Chicago
Zheng, Y., Sang, M., Liu, F., Gu, L., Li, J., Wu, Y., Shan, B."Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor". Oncology Reports 50, no. 1 (2023): 131. https://doi.org/10.3892/or.2023.8568
Copy and paste a formatted citation
x
Spandidos Publications style
Zheng Y, Sang M, Liu F, Gu L, Li J, Wu Y and Shan B: Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor. Oncol Rep 50: 131, 2023.
APA
Zheng, Y., Sang, M., Liu, F., Gu, L., Li, J., Wu, Y., & Shan, B. (2023). Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor. Oncology Reports, 50, 131. https://doi.org/10.3892/or.2023.8568
MLA
Zheng, Y., Sang, M., Liu, F., Gu, L., Li, J., Wu, Y., Shan, B."Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor". Oncology Reports 50.1 (2023): 131.
Chicago
Zheng, Y., Sang, M., Liu, F., Gu, L., Li, J., Wu, Y., Shan, B."Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor". Oncology Reports 50, no. 1 (2023): 131. https://doi.org/10.3892/or.2023.8568
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team