Huang Qiang

ABCG2 is related with the grade of glioma and resistance to mitoxantone, a chemotherapeutic drug for glioma

ObjectiveThe aim of this study is to explore if ABCG2 is related to the grade of glioma and resistance to chemotherapeutic drug for glioma.MethodsThe ABCG2 expression and distribution among glioma tissues of different grades and other samples were examined using tissue microarray technique. The enhancement of sensitivity of CD133+ glioma stem cells to chemotherapeutic agent, mitoxantone through addition of ABCG2 competitive inhibitor nicardipine was testified by MTT assay and FACS analysis.ResultsThe positive immunostaining of ABCG2 was observed in less than 10% of low-grade gliomas (3/31 in grade Ixa0+xa0II) and in more than 40% of high-grade gliomas (16/37 in grade IIIxa0+xa0IV), which was statistically different (χ2xa0=xa010.710, Pxa0=xa00.0011). In samples consisting of glioma stem cells (CD133+), the positive-straining rate was 100% (4/4), while in CD133− fraction, no positive staining was observed. A simultaneous treatment of CD133+ tumor cells with concentration-dependent mitoxantone (10−5–1xa0µM) and 2.5/5.0xa0µM nicardipine resulted in synergistic cytotoxicity. The apoptotic rate of CD133+ cells treated with mitoxantone plus nicardipine was significantly higher than that treated with mitoxantone alone (58.54xa0±xa07.06% vs. 30.7xa0±xa03.79%, Pxa0<xa00.01).ConclusionsOur results showed that ABCG2 is also expressed in glioma stem cells and the expression level of ABCG2 is positively associated with the increasing pathological grade of glioma (poor cell differentiation). ABCG2 plays a key role in glioma cells resistance to mitoxantone, chemotherapeutic drug for glioma. Thus, inhibition of ABCG2 protein activity by nicardipine in glioma can sensitize it to mitoxantone, which may lead to better treatment strategies for cancers.