he chemokine receptor CXCR4 is overexpressed and functional in colorectal cancer. To investigate the role of CXCR4 antagonism in potentiating colon cancer standard therapy, the new peptide CXCR4 antagonist Peptide R (Pep R) was employed. Human colon cancer HCT116 xenograft-bearing mice were treated with chemotherapeutic agents (CT) 5-Fluorouracil (5FU) and oxaliplatin (OX) or 5FU and radio chemotherapy (RT-CT) in the presence of Pep R. After two weeks, CT plus Pep R reduced by 4-fold the relative tumor volume (RTV) as compared to 2- and 1.6-fold reductions induced, respectively, by CT and Pep R. In vitro Pep R addition to CT/RT-CT impaired HCT116 cell growth and further reduced HCT116 and HT29 clonal capability. Thus, the hypothesis that Pep R could target the epithelial mesenchyme transition (EMT) process was evaluated. While CT decreased ECAD and increased ZEB-1 and CD90 expression, the addition of Pep R restored the pretreatment expression. In HCT116 and HT29 cells, CT/RT-CT induced a population of CD133+CXCR4+ cells, supposedly a stem-resistant cancer cell population, while Pep R reduced it. Taken together, the results showed that targeting CXCR4 ameliorates the effect of treatment in colon cancer through inhibition of cell growth and reversal of EMT treatment-induced markers, supporting further clinical studies.

New CXCR4 Antagonist Peptide R (Pep R) Improves Standard Therapy in Colorectal Cancer / D'Alterio, Crescenzo; Zannetti, Antonella; Trotta Anna, Maria; Ierano, Caterina; Napolitano, Maria; Rea, Giuseppina; Greco, Adelaide; Maiolino, Piera; Albanese, Sandra; Scognamiglio, Giosue; Tatangelo, Fabiana; Tafuto, Salvatore; Portella, Luigi; Santagata, Sara; Nasti, Guglielmo; Ottaiano, Alessandro; Pacelli, Roberto; Delrio, Paolo; Botti, Gerardo; Scala, Stefania. - In: CANCERS. - ISSN 2072-6694. - 12:7(2020), pp. 1-16. [10.3390/cancers12071952]

New CXCR4 Antagonist Peptide R (Pep R) Improves Standard Therapy in Colorectal Cancer

Zannetti Antonella
Methodology
;
Rea Giuseppina
Supervision
;
Greco Adelaide
Investigation
;
Albanese Sandra;Santagata Sara;Pacelli Roberto
Resources
;
2020

Abstract

he chemokine receptor CXCR4 is overexpressed and functional in colorectal cancer. To investigate the role of CXCR4 antagonism in potentiating colon cancer standard therapy, the new peptide CXCR4 antagonist Peptide R (Pep R) was employed. Human colon cancer HCT116 xenograft-bearing mice were treated with chemotherapeutic agents (CT) 5-Fluorouracil (5FU) and oxaliplatin (OX) or 5FU and radio chemotherapy (RT-CT) in the presence of Pep R. After two weeks, CT plus Pep R reduced by 4-fold the relative tumor volume (RTV) as compared to 2- and 1.6-fold reductions induced, respectively, by CT and Pep R. In vitro Pep R addition to CT/RT-CT impaired HCT116 cell growth and further reduced HCT116 and HT29 clonal capability. Thus, the hypothesis that Pep R could target the epithelial mesenchyme transition (EMT) process was evaluated. While CT decreased ECAD and increased ZEB-1 and CD90 expression, the addition of Pep R restored the pretreatment expression. In HCT116 and HT29 cells, CT/RT-CT induced a population of CD133+CXCR4+ cells, supposedly a stem-resistant cancer cell population, while Pep R reduced it. Taken together, the results showed that targeting CXCR4 ameliorates the effect of treatment in colon cancer through inhibition of cell growth and reversal of EMT treatment-induced markers, supporting further clinical studies.
2020
New CXCR4 Antagonist Peptide R (Pep R) Improves Standard Therapy in Colorectal Cancer / D'Alterio, Crescenzo; Zannetti, Antonella; Trotta Anna, Maria; Ierano, Caterina; Napolitano, Maria; Rea, Giuseppina; Greco, Adelaide; Maiolino, Piera; Albanese, Sandra; Scognamiglio, Giosue; Tatangelo, Fabiana; Tafuto, Salvatore; Portella, Luigi; Santagata, Sara; Nasti, Guglielmo; Ottaiano, Alessandro; Pacelli, Roberto; Delrio, Paolo; Botti, Gerardo; Scala, Stefania. - In: CANCERS. - ISSN 2072-6694. - 12:7(2020), pp. 1-16. [10.3390/cancers12071952]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/817154
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