Title |
Anti-miR21 oligonucleotide enhances chemosensitivity of T98G cell line to doxorubicin by inducing apoptosis.
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Published in |
American Journal of Cancer Research, December 2014
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Pubmed ID | |
Authors |
Laura Giunti, Martina da Ros, Serena Vinci, Stefania Gelmini, Anna Lisa Iorio, Anna Maria Buccoliero, Stefania Cardellicchio, Francesca Castiglione, Lorenzo Genitori, Maurizio de Martino, Sabrina Giglio, Maurizio Genuardi, Iacopo Sardi |
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. |
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 13 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 5 | 38% |
Student > Doctoral Student | 2 | 15% |
Researcher | 2 | 15% |
Student > Postgraduate | 1 | 8% |
Student > Bachelor | 1 | 8% |
Other | 2 | 15% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 4 | 31% |
Agricultural and Biological Sciences | 4 | 31% |
Biochemistry, Genetics and Molecular Biology | 3 | 23% |
Unspecified | 2 | 15% |