Dual‑targeted therapeutic strategy combining CSC–DC‑based vaccine and cisplatin overcomes chemo‑resistance in experimental mice model

N. E. El-Ashmawy; M.L. Salem; E.G. Khedr; E. A. El-Zamarany; A.O. Ibrahim

Ayuda

Dual‑targeted therapeutic strategy combining CSC–DC‑based vaccine and cisplatin overcomes chemo‑resistance in experimental mice model

N. E. El Ashmawy ^[1] ; M. L. Salem ^[1] ; E. G. Khedr ^[1] ; E. A. El Zamarany ^[1] ; A. O. Ibrahim ^[1]
1. [1] Tanta University
  
  Tanta University
  
  Egipto
Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 7, 2020, págs. 1155-1165
Idioma: inglés
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Resumen
- Background and purposeEmerging evidence suggests that one of the main reasons of chemotherapy treatment failure is the development of multi-drug resistance (MDR) associated with cancer stem cells (CSCs). Our aim is to identify a therapeutic strategy based on MDR-reversing agents.Materials and methodsCSC-enriched Ehrlich carcinoma (EC) cell cultures were prepared by drug-resistant selection method using different concentrations of cisplatin (CIS). Cell cultures following drug exposure were analyzed by flow cytometry for CSC surface markers CD44+/CD24−. We isolated murine bone marrow-derived dendritic cells (DCs) and then used them to prepare CSC–DC vaccine by pulsation with CSC-enriched lysate. DCs were examined by flow cytometry for phenotypic markers. Solid Ehrlich carcinoma bearing mice were injected with the CSC–DC vaccine in conjunction with repeated low doses of CIS. Tumor growth inhibition was evaluated and tumor tissues were excised and analyzed by real-time PCR to determine the relative gene expression levels of MDR and Bcl-2. Histopathological features of tumor tissues excised were examined.Results and conclusionCo-treatment with CSC–DC and CIS resulted in a significant tumor growth inhibition. Furthermore, the greatest response of downregulation of MDR and Bcl-2 relative gene expression were achieved in the same group. In parallel, the histopathological observations demonstrated enhanced apoptosis and absence of mitotic figures in tumor tissues of the co-treatment group. Dual targeting of resistant cancer cells using CSC–DC vaccine along with cisplatin represents a promising therapeutic strategy that could suppress tumor growth, circumvent MDR, and increase the efficacy of conventional chemotherapies.