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.
Cisplatin/therapeutic use , Ovarian Neoplasms/drug therapy , Receptors, Interleukin-8B/antagonists & inhibitors , Animals , Cell Line, Tumor , Cell Nucleus/drug effects , Cell Nucleus/metabolism , 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 , Ovarian Neoplasms/pathology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Interleukin-8B/metabolism , Survival Analysis , TOR Serine-Threonine Kinases/metabolism
