Eicosapentaenoic acid enhances the sensitivity of glioma cell line U87 to temozolomide via inhibiting endoplasmic reticulum stress
10.3760/cma.j.issn.1674-635X.2017.06.005
- VernacularTitle:内质网应激反应在二十碳五烯酸对胶质瘤U87细胞替莫唑胺化疗敏感性影响中的作用
- Author:
Tianzao HUANG
1
;
Xiangrong CHEN
;
Chubin LIU
;
Yanlei GAO
;
Weipeng HU
Author Information
1. 福建医科大学附属第二医院神经外科
- Keywords:
Glioma;
Eicosapentaenoic acid;
Temozolomide;
Endoplasmic reticulum stress
- From:
Chinese Journal of Clinical Nutrition
2017;25(6):361-365
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of Eicosapentaenoic scid (EPA) on the sensitivity of glioma cell line U87 to temozolomide (TMZ) and the mechanism behind this effect.Methods U87 cells were randomly divided into four groups:control group,TMZ group,EPA+TMZ group and endoplasmic reticulum stress (ERS) activation tunicamycin group (EPA+TMZ+TM group).MTT method was used to evaluate inhibition ratio of cell proliferation.The apoptotic ratio was examined by flow eytometry.Western blot was used to detect the protein expressions of apoptosis cytokines (caspase-3 and Bax) and ERS cytokines [glucose-regulated protein 78 (GRP78) and inositol-requiring enzyme 1 (IRE-1)].Results EPA causes concentration-dependent and time-dependent inhibition of the cell proliferation (all P=0.00).EPA significantly enhanced the sensitivity of glioma cell line U87 to temozolomide.Compared to TMZ treatment alone,the inhibition ratio [(56.27+6.15)％ vs.(42.32±4.12)％,P=0.03] and apoptotic ratio [(49.78±5.94)％ vs.(37.74± 4.24)％,P=0.04] of U87 cells were enhanced by EPA+TMZ treatment.Western blot showed that the expression of apoptotic factor caspase-3 and Bax proteins were increased by EPA+TMZ treatment,while the protein expressions of ERS-related factors (GRP78 and IRE-1) were significantly inhibited (P=0.01).However,the salutary effects of EPA were reversed by ERS activation tunicamycin.Conclusion EPA enhances the sensitivity of glioma cell line U87 to temozolomide,the mechanism of which may be the suppression of ERS response.
