Abstract |
Doxorubicin (DOX) is a key chemotherapeutic drug for cancer treatment. The antitumor mechanism of DOX is its action as a topoisomerase II poison by preventing DNA replication. Our study shows that DOX can be involved in epigenetic regulation of gene transcription through downregulation of DNA methyltransferase 1 (DNMT1) then reactivation of DNA methylation-silenced tumor suppressor genes in glioblastoma (GBM). Recent evidence demonstrated that microRNA (miR or miRNA) can mediate expression of genes through post-transcriptional regulation and modulate sensitivity to anticancer drugs. As one of the first miRNAs detected in the human genome, miR-21 has been validated to be overexpressed in GBM. Combination treatment of a chemotherapeutic and miRNA showed synergistically increased anticancer activities which has been proven to be an effective strategy for tumor therapy. In our study, co-treatment of DOX and miR-21 inhibitor (miR-21i) resulted in remarkably increased expression of tumor suppressor genes compared with DOX or the miR-21i treatment alone. Moreover, we demonstrate that combining DOX and miR-21i significantly reduced tumor cell proliferation, invasion and migration in vitro. Our study concludes that combining DOX and miR-21i is a new strategy for the therapy of GBM.
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Authors | Shanshan Zhang, Lei Han, Jianwei Wei, Zhendong Shi, Peiyu Pu, Jianning Zhang, Xubo Yuan, Chunsheng Kang |
Journal | International journal of oncology
(Int J Oncol)
Vol. 46
Issue 4
Pg. 1589-600
(Apr 2015)
ISSN: 1791-2423 [Electronic] Greece |
PMID | 25625875
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antibiotics, Antineoplastic
- MIRN21 microRNA, human
- MicroRNAs
- Doxorubicin
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Topics |
- Antibiotics, Antineoplastic
(pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
- Brain Neoplasms
(drug therapy, genetics)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Doxorubicin
(pharmacology)
- Drug Synergism
- Gene Expression Regulation, Neoplastic
(drug effects)
- Genes, Tumor Suppressor
(drug effects)
- Glioblastoma
(drug therapy, genetics)
- Humans
- MicroRNAs
(antagonists & inhibitors, genetics)
- Up-Regulation
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