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Article

β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells

  • Authors:
    • Ting-Zhun Zhu
    • Xiao-Ming Li
    • Li-Han Luo
    • Ying-Hui  Xu
    • Peng Cao
    • Yang Liu
    • Guo-Biao Liang
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The General Hospital of Shenyang Military Region, Shenyang, Liaoning 110840, P.R. China, Health Care Centre, Shenyang Entry-Exit Inspection and Quarantine Bureau, Shenyang, Liaoning 110016, P.R. China, Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
  • Pages: 1122-1128
    |
    Published online on: May 27, 2014
       https://doi.org/10.3892/mmr.2014.2273
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Abstract

β-elemene, a plant-derived drug extracted from Curcuma wenyujin, has demonstrated marked antiproliferative effects on glioblastoma, while toxicity remains low. However, the underlying molecular mechanisms of the antitumor activity of β-elemene remain to be elucidated. Previously, it was identified that the glia maturation factor β (GMFβ)/mitogen-activated protein kinase kinase (MAPK) 3/6/p38 pathway participates in the antiproliferative activity of β-elemene on glioblastoma. In the present study, in order to illustrate the association of GMFβ and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, U87 and U251 cells were treated with β-elemene at various doses and for different durations, and the expression of phosphorylated ERK1/2 (p-ERK1/2), ERK1/2, B-cell lymphoma 2 (Bcl-2), Bcl2-associated X and survivin was examined by western blot analysis. Following treatment with β-elemene and the ERK1/2 inhibitor PD98059, U87 cell viability was evaluated using a Cell Counting Kit-8 (CCK-8) assay, and the expression levels of Bcl-2 and survivin were examined by western blot analysis. GMFβ was then downregulated by RNA interference in β-elemene-treated U87 cells, and the effect of this on the expression of ERK1/2 and p-ERK1/2 was determined by western blot analysis. Finally, the chemosensitisation of U87 cells to temozolomide (TMZ) through β-elemene was examined using the CCK-8 assay. The results demonstrated that β-elemene inhibited the proliferation of U87 glioblastoma cells through the GMFβ‑dependent inactivation of the ERK1/2-Bcl-2/survivin pathway. Furthermore, inhibition of ERK1/2 by PD98059 enhanced the antitumor effect of β-elemene and impaired the expression levels of Bcl-2 and survivin. β-elemene also increased the sensitivity of U87 glioblastoma cells to the chemotherapeutic TMZ, which was synergistically enhanced by PD98059. In conclusion, these results suggested that GMFβ-dependent inactivation of the ERK1/2-Bcl-2/survivin pathway mediated the antiproliferative effect of β-elemene on glioblastoma. Therefore, β-elemene is a promising chemosensitizer or adjuvant therapeutic for TMZ against glioblastoma brain tumors.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu T, Li X, Luo L, Xu Y, Cao P, Liu Y and Liang G: β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells. Mol Med Rep 10: 1122-1128, 2014.
APA
Zhu, T., Li, X., Luo, L., Xu, Y., Cao, P., Liu, Y., & Liang, G. (2014). β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells. Molecular Medicine Reports, 10, 1122-1128. https://doi.org/10.3892/mmr.2014.2273
MLA
Zhu, T., Li, X., Luo, L., Xu, Y., Cao, P., Liu, Y., Liang, G."β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells". Molecular Medicine Reports 10.2 (2014): 1122-1128.
Chicago
Zhu, T., Li, X., Luo, L., Xu, Y., Cao, P., Liu, Y., Liang, G."β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells". Molecular Medicine Reports 10, no. 2 (2014): 1122-1128. https://doi.org/10.3892/mmr.2014.2273
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu T, Li X, Luo L, Xu Y, Cao P, Liu Y and Liang G: β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells. Mol Med Rep 10: 1122-1128, 2014.
APA
Zhu, T., Li, X., Luo, L., Xu, Y., Cao, P., Liu, Y., & Liang, G. (2014). β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells. Molecular Medicine Reports, 10, 1122-1128. https://doi.org/10.3892/mmr.2014.2273
MLA
Zhu, T., Li, X., Luo, L., Xu, Y., Cao, P., Liu, Y., Liang, G."β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells". Molecular Medicine Reports 10.2 (2014): 1122-1128.
Chicago
Zhu, T., Li, X., Luo, L., Xu, Y., Cao, P., Liu, Y., Liang, G."β-Elemene inhibits proliferation through crosstalk between glia maturation factor β and extracellular signal‑regulated kinase 1/2 and impairs drug resistance to temozolomide in glioblastoma cells". Molecular Medicine Reports 10, no. 2 (2014): 1122-1128. https://doi.org/10.3892/mmr.2014.2273
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