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

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

来源：International Journal of Oncology, 2016, 48(3): 1029-1038.

DOI：10.3892/ijo.2015.3308

• peptide nucleic acids
• glioma
• microRNAs
• miR-221
• miR-222
• miRNA targeting
• delivery

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.

• 出版日期2016-3