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

Zhang,Shanshan; Han,Lei; Wei,Jianwei; Shi,Zhendong; Pu,Peiyu; Zhang,Jianning; Yuan,Xubo; Kang,Chunsheng

doi:10.3892/ijo.2015.2841

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

Authors:
- Shanshan Zhang
- Lei Han
- Jianwei Wei
- Zhendong Shi
- Peiyu Pu
- Jianning Zhang
- Xubo Yuan
- Chunsheng Kang
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Affiliations: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, P.R. China, Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
Published online on: January 22, 2015 https://doi.org/10.3892/ijo.2015.2841
Pages: 1589-1600

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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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