Anti-miR21 oligonucleotide enhances chemosensitivity of T98G cell line to doxorubicin by inducing apoptosis

Maurizio Genuardi, Giunti Laura, Ros Martina Da, Vinci Serena, Gelmini Stefania, Iorio Anna Lisa, Buccoliero Anna Maria, Cardellicchio Stefania, Castiglione Francesca, Genitori Lorenzo, Martino Maurizio De, Giglio Sabrina, Sardi Iacopo

Risultato della ricerca: Contributo in rivistaArticolo in rivista


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.
Lingua originaleEnglish
pagine (da-a)231-242
Numero di pagine12
RivistaAmerican Journal of Cancer Research
Stato di pubblicazionePubblicato - 2014


  • miRNA, glioblastoma multiforme, expression analysis, CNS tumors, pediatric brain tumors


Entra nei temi di ricerca di 'Anti-miR21 oligonucleotide enhances chemosensitivity of T98G cell line to doxorubicin by inducing apoptosis'. Insieme formano una fingerprint unica.

Cita questo