title: Combination treatment with doxorubicin and microRNA-21 inhibitor synergistically augments anticancer activity through upregulation of tumor suppressing genes.
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.
authors.affiliation: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, P.R. China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wei
authors.affiliation: Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Peiyu
authors.initials: P
authors.lastname: Pu
authors.affiliation: Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, Tianjin 300072, P.R. China.
authors.forename: Xubo
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Laboratory of Neuro-Oncology, Department of Neurosurgery, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China.
authors.forename: Chunsheng
authors.initials: C
authors.lastname: Kang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000187:drug effects*; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics; D015854:Up-Regulation
chemical_list: D000903:Antibiotics, Antineoplastic; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin