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Oncotarget. 2017 Jun 6;8(23):37511-37524. doi: 10.18632/oncotarget.16400.

Promoting oligodendroglial-oriented differentiation of glioma stem cell: a repurposing of quetiapine for the treatment of malignant glioma.

Author information

1
Department of Histology and Embryology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
2
Department of Pathology, Southwest Hospital, Chongqing 400038, China.
3
Department of Neurosurgery, Southwest Hospital, Chongqing 400038, China.
4
Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Portland, OR 97232, USA.

Abstract

As a major contributor of chemotherapy resistance and malignant recurrence, glioma stem cells (GSCs) have been proposed as a target for the treatment of gliomas. To evaluate the therapeutic potential of quetiapine (QUE), an atypical antipsychotic, for the treatment of malignant glioma, we established mouse models with GSCs-initiated orthotopic xenograft gliomas and subcutaneous xenograft tumors, using GSCs purified from glioblastoma cell line GL261. We investigated antitumor effects of QUE on xenograft gliomas and its underlying mechanisms on GSCs. Our data demonstrated that (i) QUE monotherapy can effectively suppress GSCs-initiated tumor growth; (ii) QUE has synergistic effects with temozolomide (TMZ) on glioma suppression, and importantly, QUE can effectively suppress TMZ-resistant (or -escaped) tumors generated from GSCs; (iii) mechanistically, the anti-glioma effect of QUE was due to its actions of promoting the differentiation of GSCs into oligodendrocyte (OL)-like cells and its inhibitory effect on the Wnt/β-catenin signaling pathway. Together, our findings suggest an effective approach for anti-gliomagenic treatment via targeting OL-oriented differentiation of GSCs. This also opens a door for repurposing QUE, an FDA approved drug, for the treatment of malignant glioma.

KEYWORDS:

Wnt/β-catenin signaling pathway; differentiation; glioma stem cell; proliferation; quetiapine

PMID:
28415586
PMCID:
PMC5514926
DOI:
10.18632/oncotarget.16400
[Indexed for MEDLINE]
Free PMC Article

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