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- Title
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
- 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.
- Subjects
ANTI-estrogenic diet; ESTROGEN replacement therapy; SEX hormones; PHYSIOLOGY; STEROID receptors
- Publication
Molecular Medicine Reports, 2015, Vol 11, Issue 2, p1516
- ISSN
1791-2997
- Publication type
Article
- DOI
10.3892/mmr.2014.2811