Synergistic effects of the combined treatment of U251 and T98G glioma cells with an anti‑tubulin tetrahydrothieno[2,3‑c]pyridine derivative and a peptide nucleic acid targeting miR‑221‑3p

• DOI: 10.3892/ijo.2021.5241
• Publication Date: 2021-07-06T06:53:37Z
• Authors: Matteo Zurlo; Romeo Romagnoli; Paola Oliva; Jessica Gasparello; Alessia Finotti; Roberto Gambari
• Keywords: Peptide nucleic acid

In the development of novel and more effective anticancer approaches, combined treatments appear to be great interest, based on possibility obtaining relevant biological or therapeutic effects using lower concentrations single drugs. Combination therapy may prove utmost significance in management glioblastoma (GBM), a lethal malignancy that accounts for 42% cancer cases central nervous system, with median survival rate 15 months. As regards authors have recently demonstrated peptide nucleic acids (PNAs) target microRNA (miRNA/miR)‑221 are very active inducing apoptosis glioma cells. Furthermore, recent study, described two series tubulin polymerization inhibitors 4,5,6,7‑tetrahydrothieno[2,3‑c]pyridine 4,5,6,7‑tetrahydrobenzo[b]thiophene scaffold, which exerted potent anti‑proliferative effect variety tumor cell lines. The present study aimed verify activity lines one most compounds tested, corresponding 2‑(3', 4', 5'‑trimethoxyanilino)‑3‑cyano/alkoxycarbonyl‑6‑substituted‑4 5,6,7‑tetrahydrothiene[2,3‑c] pyridine (compound 3b), used combination an anti‑miR‑221‑3p PNA, already able induce high levels apoptosis. To best our knowledge, results obtained herein demonstrate first time 'combination therapy' performed by use PNA targeting miR‑221 tetrahydrothiene[2,3‑c]pyridine derivative 3b, supporting concept treatment GBM cells against specific upregulated oncomiRNA (in miR‑221‑3p was used) anti‑tubulin agents 3b is encouraging strategy enhance efficacy therapies at same time, reduce side‑effects.