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Biomed Pharmacother ; 83: 229-240, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27372407

RESUMO

Overexpression of IL17RB is associated with poor prognosis and short survival of the breast cancer patients.IL17RB/IL17B signaling triggers a substantial increase in the cell growth, proliferation and migration through the activation of NF-κB as well as the up-regulation of the Bcl-2. In this study we designed carboxymethyl dextran (CMD) Chitosan nanoparticles (ChNPs) to encapsulated IL17RB siRNA and doxorubicin (DOX) as an anticancer drug. Then we investigated the efficiency of the simultaneous delivery of drug/siRNA on viability and gene expression of MDA-MB361 cell lines. Furthermore the efficacy of dual agent nanoparticles to induce apoptosis and inhibit migration of breast cancer cells was assessed by Annexin-V and wound healing assays respectively. Our results showed that DOX-siRNA-CMD-ChNPs had about 114nm size; with polydispersity index and zeta potential about 0.3 and 10.1mV respectively. Fourier transform infrared spectroscopy (FTIR) confirmed the formation of DOX-siRNA-CMD-ChNPs complex. In addition IL17RB siRNA had significant effect on DOX-induced cytotoxicity in MDA-MB361 cells. Furthermore treatment with dual agent nanoparticles resulted in a significant silencing of NF-κB and Bcl-2 relative gene expression, apoptosis induction and migration inhibition in MDA-MB361 cells. In conclusion, co-delivery of IL17RB siRNA and DOX can be considered as an effective system for the treatment of breast cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quitosana/análogos & derivados , Doxorrubicina/uso terapêutico , Sistemas de Liberação de Medicamentos , Nanopartículas/química , RNA Interferente Pequeno/metabolismo , Receptores de Interleucina-17/metabolismo , Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Quitosana/química , Doxorrubicina/farmacologia , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Heparina/metabolismo , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Soro/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Cicatrização/efeitos dos fármacos
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