Inhibition of CXCR2 plays a pivotal role in re-sensitizing ovarian cancer to cisplatin treatment.
Animals
Cell Line, Tumor
Cell Nucleus
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Chemokine CXCL2
/ metabolism
Chick Embryo
Cisplatin
/ pharmacology
Drug Resistance, Neoplasm
/ drug effects
Epithelial-Mesenchymal Transition
/ drug effects
Female
Humans
MAP Kinase Signaling System
/ drug effects
Neoplasm Invasiveness
Neoplasm Proteins
/ metabolism
Neovascularization, Pathologic
/ drug therapy
Ovarian Neoplasms
/ blood supply
Phosphatidylinositol 3-Kinases
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Receptors, Interleukin-8B
/ antagonists & inhibitors
Survival Analysis
TOR Serine-Threonine Kinases
/ metabolism
CXCR2
chemoresistance
high grade serous ovarian cancer
tumor microenvironment
Journal
Aging
ISSN: 1945-4589
Titre abrégé: Aging (Albany NY)
Pays: United States
ID NLM: 101508617
Informations de publication
Date de publication:
26 05 2021
26 05 2021
Historique:
received:
23
09
2020
accepted:
21
01
2021
pubmed:
27
5
2021
medline:
23
7
2021
entrez:
26
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34038868
pii: 203074
doi: 10.18632/aging.203074
pmc: PMC8202899
doi:
Substances chimiques
Chemokine CXCL2
0
Neoplasm Proteins
0
Receptors, Interleukin-8B
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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