Neurokinin-1 receptor is highly expressed in cervical cancer and its antagonist induces cervical cancer cell apoptosis

Liyun Guan; Shifa Yuan; Jing Ma; Hong Liu; Lizhen Huang; Fengzhen Zhang

doi:10.4081/ejh.2023.3570

Authors

Liyun Guan

Department of Oncology, The Third Hospital of Shijiazhuang, China.

Shifa Yuan

Department of General Surgery, Hospital of Hebei Province Crop of Chinese Armed Police Force, Shijiazhuang, China.

Jing Ma

shj911la@gmail.com

Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Hong Liu

Department of Gynecology and Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Lizhen Huang

Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang , China.

Fengzhen Zhang

Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Neurokinin-1 receptor (NK1R) belongs to tachykinin receptor family. Recent studies have suggested that NK1R was upregulated in cancer tissues including breast cancer, glioma and melanoma. Furthermore, NK1R antagonists have been employed to exert anti-tumor effect and promote cancer cell apoptosis. However, the role of NK1R in cervical cancer remains largely unknown. In this study, we aimed to detect the expression of NK1R in cervical cancer and evaluate the anti-tumor effects of NK1R antagonist on cervical cancer cells. We found that NK1R was highly expressed in cervical cancer tissues than in adjacent normal cervical tissues. Furthermore, by using NK1R antagonist we demonstrated that NK1R antagonist inhibited the viability and induced the apoptosis of cervical cancer cells in a dose-dependent manner, and the mechanism may be related to the inhibition of ERK activation and the regulation of apoptosis proteins Bcl-2 and BAX. In conclusion, these findings suggest that NK1R plays an oncogenic role in cervical cancer and is a promising target for cervical cancer therapy.

Altmetrics

Downloads

Citations

Halim A, Mustafa WA, Khairunizam W, Rahim HA, Sakeran H. Nucleus detection on pap smear images for cervical cancer diagnosis: A Review Analysis. Oncologie 2021;23:73-88. DOI: https://doi.org/10.32604/Oncologie.2021.015154

Sundaram MK, Almutary AG, Haque S, Faheem SM, Arif Hussain A. Awareness of human papilloma virus and its association with cervical cancer among female university students: A study from United Arab Emirates. Oncologie 2021;23:269-77. DOI: https://doi.org/10.32604/Oncologie.2021.016002

Gao W, Ma Q, Tang C, Zhan Y, Duan Y, Ni H, et al. Microenvironment and related genes predict outcomes of patients with cervical cancer: evidence from TCGA and bioinformatic analysis. Biocell 2020;44:597-605. DOI: https://doi.org/10.32604/biocell.2020.011328

Liu Y, An S, Ward R, Yang Y, Guo XX, Li W, et al. G protein-coupled receptors as promising cancer targets. Cancer Lett 2016;376:226-39. DOI: https://doi.org/10.1016/j.canlet.2016.03.031

Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: new agents, targets and indications. Nat Rev Drug Disc 2017;16:829–42. DOI: https://doi.org/10.1038/nrd.2017.178

Douglas SD, Leeman SE. Neurokinin-1 receptor: functional significance in the immune system in reference to selected infections and inflammation. Ann N Y Acad Sci 2011;1217:83-95. DOI: https://doi.org/10.1111/j.1749-6632.2010.05826.x

Majkowska-Pilip AA-O, Halik PA-O, Gniazdowska EA-O. The significance of NK1 receptor ligands and their application in targeted radionuclide tumour therapy. Pharmaceutics 2019;11:443. DOI: https://doi.org/10.3390/pharmaceutics11090443

Wang F, Liu S, Liu J, Feng F, Guo Y, Zhang W, et al. SP promotes cell proliferation in esophageal squamous cell carcinoma through the NK1R/Hes1 axis. Biochem Biophys Res Commun 2019;514:1210–6.

Huang C, Li Y, Guo Y, Zhang Z, Lian G, Chen Y, et al. MMP1/PAR1/SP/NK1R paracrine loop modulates early perineural invasion of pancreatic cancer cells. Theranostics 2018;8:3074-86. DOI: https://doi.org/10.7150/thno.24281

Deng XT, Tang SM, Wu PY, Li QP, Ge XX, Xu BM, et al. SP/NK-1R promotes gall bladder cancer cell proliferation and migration. J Cell Mol Med 2019;23:7961-73. DOI: https://doi.org/10.1111/jcmm.14230

Bayati S, Bashash D, Ahmadian S, Safaroghli-Azar A, Alimoghaddam K, Ghavamzadeh A, et al. Inhibition of tachykinin NK1 receptor using aprepitant induces apoptotic cell death and G1 arrest through Akt/p53 axis in pre-B acute lymphoblastic leukemia cells. Eur J Pharm 2016;791:274-83. DOI: https://doi.org/10.1016/j.ejphar.2016.09.006

Javid H, Asadi J, Zahedi Avval F, Afshari AR, Hashemy SI. 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. Mol Biol Rep 2020;47:2253-63. DOI: https://doi.org/10.1007/s11033-020-05330-9

Mozafari M, Ebrahimi S, Darban RA, Hashemy SI. Potential in vitro therapeutic effects of targeting SP/NK1R system in cervical cancer. Mol Biol Rep 2022;49:1067-76. DOI: https://doi.org/10.1007/s11033-021-06928-3

Wang F, Liu S, Liiu J, Feng F, Guo Y, Zhang W, et al. SP promotes cell proliferation in esophageal squamous cell carcinoma through the NK1R/Hes1 axis. Biochem Biophys Res Commun 2019;514:1210-6. DOI: https://doi.org/10.1016/j.bbrc.2019.05.092

Nizam E, Erin N. Differential consequences of neurokinin receptor 1 and 2 antagonisits in metastatic breast carcinoma cells. Effects independent of substance P. Biomed Pharmacother 2018;108:263-70. DOI: https://doi.org/10.1016/j.biopha.2018.09.013

Gharaee N, Pourali L, Jafarian AH, Hashemy SI. Evaluation of serum level of substance P and tissue distribution of NK-1 receptor in endometrial cancer. Mol Biol Rep 2018;45:2257-62. DOI: https://doi.org/10.1007/s11033-018-4387-1

Ortiz-Prieto A, Bernabeu-Wittel J, Zulueta-Dorado T, Lorente-Lavirgen AI, Muñoz M. Immunolocalization of substance P and NK-1 receptor in vascular anomalies. Arch Dermatol Res 2017;309:97-102. DOI: https://doi.org/10.1007/s00403-016-1707-y

Zhang L, Wang L, Dong D, Wang Z, Ji W, Yu M, et al. MiR-34b/c-5p and the neurokin-1 receptor regulate breast cancer cell proliferation and apoptosis. Cell Prolif 2019;52:e12527. DOI: https://doi.org/10.1111/cpr.12527

Muñoz M, Rosso M, Coveñas R. The NK-1receptor antagonist L-732,138 induce apoptosis in human gastrointestinal cancer cell lines. Pharmacol Rep 2017;69:696-701. DOI: https://doi.org/10.1016/j.pharep.2017.02.002

Nizam E, Köksoy S, Erin N. NK1R antagonist decreases inflammation and metastasis of breast carcinoma cells metastasized to liver but not to brain; phenotype-dependent therapeutic and toxic consequences. Cancer Immunol Immunother 2020;69:1639-50. DOI: https://doi.org/10.1007/s00262-020-02574-z

Virtakoivu R, Mai A, Mattila E, De Franceschi N, Imanishi SY, Corthals G, et al. Vimentin-ERK signaling uncouples slug gene regulatory function. Cancer Res 2015,75:2349-62. DOI: https://doi.org/10.1158/0008-5472.CAN-14-2842

Peng Y, Li W, Chen S, Wu W, Shang Z. MiR-494-3p regulates cell proliferation and apoptosis via KLF7 in Schwann cells. Biocell 2021;45:57-64. DOI: https://doi.org/10.32604/biocell.2021.011756

Edited by

This study was approved by Ethics Committee of Hebei Medical University (approval No. 2018019)

Supporting Agencies

Hebei Province Medical Science Research Key Project Program

How to Cite

Neurokinin-1 receptor is highly expressed in cervical cancer and its antagonist induces cervical cancer cell apoptosis. (2023). European Journal of Histochemistry, 67(1). https://doi.org/10.4081/ejh.2023.3570

Download Citation

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.

Current Issue