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Research Paper Volume 13, Issue 10 pp 13405—13420

Inhibition of CXCR2 plays a pivotal role in re-sensitizing ovarian cancer to cisplatin treatment

Taciane Barbosa Henriques1, , Diandra Zipinotti dos Santos1, , Isabella dos Santos Guimarães2, , Nayara Gusmão Tessarollo1, , Paulo Cilas Morais Lyra-Junior1, , Patricia Mesquita3,4, , Diana Pádua3,4, , Ana Luisa Amaral3,4, , Bruno Cavadas3,4, , Luisa Pereira3,4, , Ian Victor Silva5,6,7, , Raquel Maria da Silva Graça Almeida3,4,8, , Leticia Batista Azevedo Rangel1,6,7, ,

  • 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, 2021      

https://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.

Abstract

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.

Abbreviations

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.

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Corresponding Author

Leticia Batista Azevedo Rangel
leticia.rangel@ufes.com

Keywords
chemoresistance high grade serous ovarian cancer CXCR2 tumor microenvironment