Combination treatment with doxorubicin and microRNA-21 inhibitor synergistically augments anticancer activity through upregulation of tumor suppressing genes.
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| 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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