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 Mesquita^3,⁴, Diana Pádua^3,⁴, Ana Luisa Amaral^3,⁴, Bruno Cavadas^3,⁴, Luisa Pereira^3,⁴, Ian Victor Silva^5,^6,⁷, Raquel Maria da Silva Graça Almeida^3,^4,⁸, Leticia Batista Azevedo Rangel^1,^6,⁷

¹Biotechnology Program/RENORBIO, Health Sciences Center, Federal University of Espirito Santo, Espirito Santo, Brazil
²Translational Research Laboratory/Division of Clinical Research and Technological Development/National Cancer Institute (INCa), Rio de Janeiro, Brazil
³Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal
⁴Institute of Pathology and Molecular Immunology (IPATIMUP), University of Porto, Porto, Portugal
⁵Department of Morphology, Health Sciences Center, Federal University of Espirito Santo, Espirito Santo, Brazil
⁶Biochemistry and Pharmacology Program, Federal University of Espirito Santo, Espirito Santo, Brazil
⁷Pharmaceutical Sciences Department, Health Sciences Center, Federal University of Espirito Santo, Espirito Santo, Brazil
⁸Biology Department, Faculty of Sciences, University of Porto, Porto, Portugal

Received: September 23, 2020Accepted: January 21, 2021Published: May 26, 2021

https://doi.org/10.18632/aging.203074

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.