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

J Cancer Res Clin Oncol. 2009 Oct;135(10):1369-76. doi: 10.1007/s00432-009-0578-4. Epub 2009 Apr 2.


Objective: The aim of this study is to explore if ABCG2 is related to the grade of glioma and resistance to chemotherapeutic drug for glioma.

Methods: The 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.

Results: The positive immunostaining of ABCG2 was observed in less than 10% of low-grade gliomas (3/31 in grade I + II) and in more than 40% of high-grade gliomas (16/37 in grade III + IV), which was statistically different (chi (2) = 10.710, P = 0.0011). 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)-1 microM) and 2.5/5.0 microM 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 (58.54 +/- 7.06% vs. 30.7 +/- 3.79%, P < 0.01).

Conclusions: Our 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / antagonists & inhibitors
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm*
  • Glioma / drug therapy*
  • Glioma / metabolism
  • Glioma / secondary
  • Humans
  • Immunoenzyme Techniques
  • Mice
  • Mice, Nude
  • Mitoxantrone / therapeutic use*
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Nicardipine / therapeutic use
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Rate
  • Tissue Array Analysis
  • Tumor Cells, Cultured
  • Vasodilator Agents / therapeutic use


  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Neoplasm Proteins
  • RNA, Messenger
  • Vasodilator Agents
  • Mitoxantrone
  • Nicardipine