Promoting Oligodendroglial-oriented Differentiation of Glioma Stem Cell: a Repurposing of Quetiapine for the Treatment of Malignant Glioma

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Apr 19

PMID 28415586

Citations 27

Authors

Yun Wang

Nanxin Huang

Hongli Li

Shubao Liu

Xianjun Chen

Shichang Yu

Nan Wu

Xiu-Wu Bian

Hai-Ying Shen

Chengren Li

Lan Xiao

Affiliations

Soon will be listed here.

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.

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