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Article

Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway

  • Authors:
    • Xiaoyang Liu
    • Libo Wang
    • Jiajun Chen
    • Qi Ling
    • Hongfei Wang
    • Shilin Li
    • Liming Li
    • Shuping Yang
    • Mingying Xia
    • Ling Jing
  • View Affiliations / Copyright

    Affiliations: School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, China‑Japan Union Hospital, Jilin University, Changchun, Jilin 130033, P.R. China, Jilin Medical College, Jilin, Jilin 132013, P.R. China, Department of Vascular Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China, MOE Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering and School of Life Sciences, Fudan University, Shanghai 200433, P.R. China
  • Pages: 1516-1522
    |
    Published online on: October 29, 2014
       https://doi.org/10.3892/mmr.2014.2811
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Abstract

Glioma is the most common primary brain tumor among adults. Temozolomide (TMZ) is widely used as the first‑line postsurgical drug for malignant glioma. However, the therapeutic efficacy of TMZ remains ineffective as inherited or acquired drug resistance is frequently observed. Estrogen receptor β (ERβ) has emerged as a tumor suppressor and a key regulator of signal transduction in glioma cells. However, little is known about the role of ERβ in regulating the chemotherapeutic response to TMZ. In the current study, the TMZ‑resistant U138 glioma cells were treated with the novel ERβ agonist liquiritigenin (Liq). It was observed that Liq significantly enhanced ERβ expression and sensitized glioma cells to TMZ‑induced proliferation inhibition. As a potential mechanism, it was noted that Liq treatment significantly inhibited the activity of the PI3K/AKT/mTOR pathway, which played a protective role against the TMZ‑induced cytotoxicity. In addition, it was demonstrated that ERβ knockdown or activation of the phosphatidylinositol‑4,5‑bisphosphate 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway by insulin‑like growth factor 1 both eradicated the function of Liq. These results suggest that Liq treatment enhances glioma cell susceptibility to TMZ by inhibiting the PI3K/AKT/mTOR pathway. As hyperactivation of the PI3K/AKT/mTOR pathway is frequently observed in gliomas, the combined use of ERβ agonists may become a feasible therapy option to overcome chemoresistance to TMZ.
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Copy and paste a formatted citation
Spandidos Publications style
Liu X, Wang L, Chen J, Ling Q, Wang H, Li S, Li L, Yang S, Xia M, Jing L, Jing L, et al: Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway. Mol Med Rep 11: 1516-1522, 2015.
APA
Liu, X., Wang, L., Chen, J., Ling, Q., Wang, H., Li, S. ... Jing, L. (2015). Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway. Molecular Medicine Reports, 11, 1516-1522. https://doi.org/10.3892/mmr.2014.2811
MLA
Liu, X., Wang, L., Chen, J., Ling, Q., Wang, H., Li, S., Li, L., Yang, S., Xia, M., Jing, L."Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway". Molecular Medicine Reports 11.2 (2015): 1516-1522.
Chicago
Liu, X., Wang, L., Chen, J., Ling, Q., Wang, H., Li, S., Li, L., Yang, S., Xia, M., Jing, L."Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway". Molecular Medicine Reports 11, no. 2 (2015): 1516-1522. https://doi.org/10.3892/mmr.2014.2811
Copy and paste a formatted citation
x
Spandidos Publications style
Liu X, Wang L, Chen J, Ling Q, Wang H, Li S, Li L, Yang S, Xia M, Jing L, Jing L, et al: Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway. Mol Med Rep 11: 1516-1522, 2015.
APA
Liu, X., Wang, L., Chen, J., Ling, Q., Wang, H., Li, S. ... Jing, L. (2015). Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway. Molecular Medicine Reports, 11, 1516-1522. https://doi.org/10.3892/mmr.2014.2811
MLA
Liu, X., Wang, L., Chen, J., Ling, Q., Wang, H., Li, S., Li, L., Yang, S., Xia, M., Jing, L."Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway". Molecular Medicine Reports 11.2 (2015): 1516-1522.
Chicago
Liu, X., Wang, L., Chen, J., Ling, Q., Wang, H., Li, S., Li, L., Yang, S., Xia, M., Jing, L."Estrogen receptor β agonist enhances temozolomide sensitivity of glioma cells by inhibiting PI3K/AKT/mTOR pathway". Molecular Medicine Reports 11, no. 2 (2015): 1516-1522. https://doi.org/10.3892/mmr.2014.2811
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