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Mol Cancer Ther. 2016 Mar;15(3):421-9. doi: 10.1158/1535-7163.MCT-15-0709. Epub 2016 Jan 28.

Tigecycline Inhibits Glioma Growth by Regulating miRNA-199b-5p-HES1-AKT Pathway.

Author information

1
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.
2
Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing, China.
3
Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing, China. Department of Neurosurgery, Second Artillery General Hospital, Chinese People's Liberation Army, Beijing, China.
4
Department of Neurosurgery, Daping Hospital, Third Military Medical University, Chongqing, China. hcui@swu.edu.cn xuliu559@163.com.
5
State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China. hcui@swu.edu.cn xuliu559@163.com.

Abstract

Tigecycline is a broad-spectrum, first-in-class glycylcycline antibiotic currently used to treat complicated skin infections and community-acquired pneumonia. However, there is accumulating evidence showing that tigecycline has anticancer properties. In this study, we found tigecycline could inhibit cell proliferation by inducing cell-cycle arrest, but not apoptosis in glioma. To find the underlying mechanism of how tigecycline inhibits cell proliferation, the expression of miRNAs, which were related to regulating cell-cycle progression, was detected with miRNA assay. We found that miR-199b-5p expression was significantly increased after tigecycline treatment, and miR-199b-5p target gene HES1 was downregulated. In addition, the PI3K/AKT pathway was inhibited and p21 expression was increased. When treated with tigecycline and miR-199b-5p antagomir simultaneously in glioma cells, we found that miR-199b-5p antagomir could partly block the effects induced by tigecycline. Tigecycline effectively upregulated miR-199b-5p expression and inhibited tumor growth in the xenograft tumor model of U87 glioma cells. These results suggest that tigecycline may induce cell-cycle arrest and inhibit glioma growth by regulating miRNA-199b-5p-HES1-AKT pathway. Thus, tigecycline is a promising agent in the treatment of malignant gliomas.

PMID:
26823491
DOI:
10.1158/1535-7163.MCT-15-0709
[Indexed for MEDLINE]
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