Combination therapy with chitosan/siRNA nanoplexes targeting PDGF-D and PDGFR-ß reveals anticancer effect in breast cancer.
J Gene Med
; 25(2): e3465, 2023 02.
Article
en En
| MEDLINE
| ID: mdl-36413571
ABSTRACT
BACKGROUND:
Platelet derived growth factors (PDGF)-D and the expression of its receptor increase in neoplastic progression of cancer. Co-silencing of growth factor and receptor can be suggested as an important strategy for effective cancer therapy. In the present study, we hypothesized that suppression of PDGF-D signaling pathway with small interfering RNAs (siRNAs) targeting both PDGF-D and PDGF receptor (PDGFR)-ß is a promising strategy for anticancer therapy.METHODS:
Chitosan nanoplexes containing dual and single siRNA were prepared at different weight ratios and controlled by gel retardation assay. Characterization, cellular uptake, gene silencing and invasion studies were performed. The effect of nanoplexes on breast tumor growth, PDGF expression and apoptosis was investigated.RESULTS:
We have shown that downregulation of PDGF-D and PDGFR-ß with chitosan/siRNA nanoplex formulations reduced proliferation and invasion in breast cancer cells. In the in vivo breast tumor model, it was determined that the intratumoral administration of chitosan/siPDGF-D/siPDGFR-ß nanoplexes markedly decreased the tumor volume and PDGF-D and PDGFR-ß mRNA and protein expression levels and increased apoptosis.CONCLUSIONS:
According to the results obtained, we evaluated the effect of PDGF-D and PDGFR-ß on breast tumor development and showed that RNAi-mediated inhibition of this pathway formulated with chitosan nanoplexes can be considered as a new breast cancer therapy strategy.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
ARN Interferente Pequeño
/
Quitosano
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
J Gene Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Turquía