title: Anti-miR21 oligonucleotide enhances chemosensitivity of T98G cell line to doxorubicin by inducing apoptosis.
abstract: Various signal transduction pathways seem to be involved in chemoresistance mechanism of glioblastomas (GBMs). miR-21 is an important oncogenic miRNA which modulates drug resistance of tumor cells. We analyzed the expression of 5 miRNAs, previously found to be dysregulated in high grade gliomas, in 9 pediatric (pGBM) and in 5 adult (aGBM) GBMs. miR-21 was over-expressed, with a significant difference between pGBMs and aGBMs represented by a 4 times lower degree of expression in the pediatric compared to the adult series (p = 0.001). Doxorubicin (Dox) seems to be an effective anti-glioma agent with high antitumor activity also against glioblastoma stem cells. We therefore evaluated the chemosensitivity to Dox in 3 GBM cell lines (A172, U87MG and T98G). Dox had a cytotoxic effect after 48 h of treatment in A172 and U87MG, while T98G cells were resistant. TUNEL assay verified that Dox induced apoptosis in A172 and U87MG but not in T98G. miR-21 showed a low basal expression in treated cells and was over-expressed in untreated cells. To validate the possible association of miR-21 with drug resistance of T98G cells, we transfected anti-miR-21 inhibitor into the cells. The expression level of miR-21 was significantly lower in T98G transfected cells (than in the parental control cells). Transfected cells showed a high apoptotic rate compared to control after Dox treatment by TUNEL assay, suggesting that combined Dox and miR-21 inhibitor therapy can sensitize GBM resistant cells to anthracyclines by enhancing apoptosis.
authors: Medical Genetics Unit, Meyer Children's University Hospital Florence, Italy.
authors: Laura
authors: L
authors: Giunti
authors: Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's University Hospital Florence, Italy.
authors: Martina
authors: M
authors: da Ros
authors: Department of Biomedical, Experimental and Clinical Sciences, University of Florence Italy.
authors: Serena
authors: S
authors: Vinci
authors: Department of Biomedical, Experimental and Clinical Sciences, University of Florence Italy.
authors: Stefania
authors: S
authors: Gelmini
authors: Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's University Hospital Florence, Italy.
authors: Anna Lisa
authors: AL
authors: Iorio
authors: Anatomic Pathology Unit, Meyer Children's University Hospital Florence, Italy.
authors: Anna Maria
authors: AM
authors: Buccoliero
authors: Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's University Hospital Florence, Italy.
authors: Stefania
authors: S
authors: Cardellicchio
authors: Anatomic Pathology Unit, Meyer Children's University Hospital Florence, Italy.
authors: Francesca
authors: F
authors: Castiglione
authors: Neurosurgery-Unit, Department of Neuroscience, Meyer Children's Hospital Florence, Italy.
authors: Lorenzo
authors: L
authors: Genitori
authors: Department of Paediatric Medicine, Meyer Children's Hospital and Department of Health Sciences, University of Florence Florence, Italy.
authors: Maurizio
authors: M
authors: de Martino
authors: Medical Genetics Unit, Meyer Children's University Hospital Florence, Italy ; Department of Clinical and Experimental Biomedical Sciences, University of Florence Florence, Italy.
authors: Sabrina
authors: S
authors: Giglio
authors: Department of Clinical and Experimental Biomedical Sciences, University of Florence Florence, Italy ; Current address: Institute of Medical Genetics, "A. Gemelli" School of Medicine, Catholic University Rome, Italy.
authors: Maurizio
authors: M
authors: Genuardi
authors: Neuro-oncology Unit, Department of Paediatric Medicine, Meyer Children's University Hospital Florence, Italy.
authors: Iacopo
authors: I
authors: Sardi
keywords: CNS tumors; expression analysis; glioblastoma multiforme; miRNA; pediatric brain tumors
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