Research Paper Volume 13, Issue 10 pp 13405—13420
Inhibition of CXCR2 plays a pivotal role in re-sensitizing ovarian cancer to cisplatin treatment
- 1 Biotechnology Program/RENORBIO, Health Sciences Center, Federal University of Espirito Santo, Espirito Santo, Brazil
- 2 Translational Research Laboratory/Division of Clinical Research and Technological Development/National Cancer Institute (INCa), Rio de Janeiro, Brazil
- 3 Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal
- 4 Institute of Pathology and Molecular Immunology (IPATIMUP), University of Porto, Porto, Portugal
- 5 Department of Morphology, Health Sciences Center, Federal University of Espirito Santo, Espirito Santo, Brazil
- 6 Biochemistry and Pharmacology Program, Federal University of Espirito Santo, Espirito Santo, Brazil
- 7 Pharmaceutical Sciences Department, Health Sciences Center, Federal University of Espirito Santo, Espirito Santo, Brazil
- 8 Biology Department, Faculty of Sciences, University of Porto, Porto, Portugal
Received: September 23, 2020 Accepted: January 21, 2021 Published: May 26, 2021https://doi.org/10.18632/aging.203074
How to Cite
Copyright: © 2021 Henriques et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
cDNA microarray data conducted by our group revealed overexpression of CXCL2 and CXCL8 in ovarian cancer (OC) microenvironment. Herein, we have proven that the chemokine receptor, CXCR2, is a pivotal molecule in re-sensitizing OC to cisplatin, and its inhibition decreases cell proliferation, viability, tumor size in cisplatin-resistant cells, as well as reversed the overexpression of mesenchymal epithelium transition markers. Altogether, our study indicates a central effect of CXCR2 in preventing tumor progression, due to acquisition of cisplatin chemoresistant phenotype by tumor cells, and patients’ high lethality rate. We found that the overexpression of CXCR2 by OC cells is persistent and anomalously confined to the cellular nuclei, thus pointing to an urge in developing highly lipophilic molecules that promptly permeate cells, bind to and inhibit nuclear CXCR2 to fight OC, instead of relying on the high-cost genetic engineered cells.
EOC: Epithelial Ovarian Cancer; HGSOC: High Grade Serous Ovarian Cancer; KD: Knockdown; EMT: Epithelial-mesenchymal transition; NC: Negative Control; OC: Ovarian cancer; TME: tumor microenvironment; OS: Overall Survival; TG: Tumor growth; CAM: Chicken embryo chorioallantoic membrane.