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Article Open Access

Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells

  • Authors:
    • Zhiyun Yu
    • Gang Zhao
    • Pengliang Li
    • Yunqian Li
    • Guangtong Zhou
    • Yong Chen
    • Guifang Xie
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Obstetrics and Gynecology, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
    Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2792-2800
    |
    Published online on: March 8, 2016
       https://doi.org/10.3892/ol.2016.4315
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Abstract

Glioblastoma is the most common and most aggressive brain tumor in adults. The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas, but it is not curative. The difficulties in treating glioblastoma may be as a result of the presence of glioma stem cells (GSCs), which are a source of relapse and chemoresistance. Another reason may be that endogenous Akt kinase activity may be activated in response to clinically relevant concentrations of TMZ. Akt activation is correlated with the increased tumorigenicity, invasiveness and stemness of cancer cells and overexpression of an active form of Akt increases glioma cell resistance to TMZ. Mounting evidence has demonstrated that cancer stem cells are preferentially sensitive to an inhibitor of Akt and down‑regulation of the PI3K/Akt pathway may enhance the cytotoxicity of TMZ. Metformin (MET), the first‑line drug for treating diabetes, it has been proved that it reduces AKT activation and selectively kills cancer stem cells, but whether it can potentiate the cytotoxicity of TMZ for GSCs remains unknown. In the present study, the GSCs isolated from human glioma cell line U87 and Rat glioma cell line C6, in vitro treatment with TMZ either alone or with MET. The present study demonstrates that MET acts synergistically with TMZ in inhibiting GSCs proliferation and generating the highest apoptotic rates when compared to either drug alone. These findings implicate that GSCs cytotoxicity mediated by TMZ may be stimulated by MET, have a synergistic effect, but the definite mechanisms remain elusive.
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Copy and paste a formatted citation
Spandidos Publications style
Yu Z, Zhao G, Li P, Li Y, Zhou G, Chen Y and Xie G: Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells. Oncol Lett 11: 2792-2800, 2016.
APA
Yu, Z., Zhao, G., Li, P., Li, Y., Zhou, G., Chen, Y., & Xie, G. (2016). Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells. Oncology Letters, 11, 2792-2800. https://doi.org/10.3892/ol.2016.4315
MLA
Yu, Z., Zhao, G., Li, P., Li, Y., Zhou, G., Chen, Y., Xie, G."Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells". Oncology Letters 11.4 (2016): 2792-2800.
Chicago
Yu, Z., Zhao, G., Li, P., Li, Y., Zhou, G., Chen, Y., Xie, G."Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells". Oncology Letters 11, no. 4 (2016): 2792-2800. https://doi.org/10.3892/ol.2016.4315
Copy and paste a formatted citation
x
Spandidos Publications style
Yu Z, Zhao G, Li P, Li Y, Zhou G, Chen Y and Xie G: Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells. Oncol Lett 11: 2792-2800, 2016.
APA
Yu, Z., Zhao, G., Li, P., Li, Y., Zhou, G., Chen, Y., & Xie, G. (2016). Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells. Oncology Letters, 11, 2792-2800. https://doi.org/10.3892/ol.2016.4315
MLA
Yu, Z., Zhao, G., Li, P., Li, Y., Zhou, G., Chen, Y., Xie, G."Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells". Oncology Letters 11.4 (2016): 2792-2800.
Chicago
Yu, Z., Zhao, G., Li, P., Li, Y., Zhou, G., Chen, Y., Xie, G."Temozolomide in combination with metformin act synergistically to inhibit proliferation and expansion of glioma stem-like cells". Oncology Letters 11, no. 4 (2016): 2792-2800. https://doi.org/10.3892/ol.2016.4315
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