Artigo Acesso aberto

High levels of apoptosis are induced in human glioma cell lines by co-administration of peptide nucleic acids targeting miR-221 and miR-222

2015; Spandidos Publishing; Volume: 48; Issue: 3 Linguagem: Inglês

10.3892/ijo.2015.3308

ISSN

1019-6439

Autores

Eleonora Brognara, Enrica Fabbri, Giulia Montagner, Jessica Gasparello, Alex Manicardi, Roberto Corradini, Nicoletta Bianchi, Alessia Finotti, Giulia Breveglieri, Monica Borgatti, Ilaria Lampronti, Roberta Milani, Maria Cristina Dechecchi, Giulio Cabrini, Roberto Gambari,

Tópico(s)

DNA and Nucleic Acid Chemistry

Resumo

The biological activity of a combined treatment of U251, U373 and T98G glioma cell lines with two anti-miR PNAs, directed against miR‑221 and miR‑222 and conjugated with an ocataarginine tail (R8-PNA-a221 and R8-PNA-a222) for efficient cellular delivery, was determined. Apoptosis was analyzed, and the effect of the combined treatment of glioma cells with either or both PNAs on the reversion of drug-resistance phenotype was assessed in the temozolomide-resistant T98G glioma cell line. Selectivity of PNA/miRNA interactions was studied by surface plasmon resonance (SPR)-based Biacore analysis. Specificity of the PNA effects at the cellular level was analyzed by RT-qPCR. These experiments support the concept that the effects of R8-PNA-a221 and R8-PNA-a222 are specific. The studies on apoptosis confirmed that the R8-PNA-a221 induces apoptosis and demonstrated the pro-apoptotic effects of R8-PNA-a222. Remarkably, increased pro-apoptotic effects were obtained with the co-administration of both anti-miR‑221 and anti-miR‑222 PNAs. In addition, co-administration of R8-PNA-a221 and R8-PNA-a222 induced apoptosis of TMZ-treated T98G cells at a level higher than that obtained following singular administration of R8-PNA-a221 or R8-PNA-a222.

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