肿瘤药学2019，Vol.9Issue(1)：26-34,9.DOI:10.3969/j.issn.2095-1264.2019.01.06
衣霉素诱导的内质网应激对人食管癌细胞自噬和凋亡的影响及其与奥沙利铂化疗耐药的关系
Effects of Tunicamycin Induced-endoplasmic Reticulum Stress on Autophagy and Apoptosis of Human Esophageal Cancer Cells and its Relationship with the Sensitivity to Oxaliplatin★
摘要
Abstract
Objective To investigate the effects of Tunicamycin (TM)-induced endoplasmic reticulum stress (ERS) on autophagy and apoptosis in human esophageal cancer (EC) cell line TE-1, and to provide clues for the occurrence of chemotherapy resistance. Meth-ods ERS model was established in TE-1 cells with TM. Western blot analysis was used to detect the expression of ERS marker protein GRP78, ERS pathway-related proteins (eIF2α, CHOP), AKT/mTOR pathway-related proteins, autophagy-related proteins (LC3-I/LC3-II, Beclin-1, p62) and apoptosis-related proteins (Bcl-2, Bax, Caspase 3). The effects of different concentrations of TM and oxaliplatin on TE-1 cell survival rate were measured by 3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide (MTT) assay. The autophagy was detected by Monodansylcadaverine (MDC), and apoptosis by flow cytometry. Results TM induced the expression of GRP78 increasing. After TM treatment, the phosphorylation levels of PERK and eIF2α increased, and the CHOP expression increased. The number of autophagic vesicles increased in a concentration-time dependent manner. Along with the increase of the concentration of TM, the expressions of LC3-I/LC3-II, Beclin-1, p62, Bax and Caspase 3 were up-regulated, while the Bcl-2 expression was down-regulated, and the phosphorylation of AKT/mTOR pathway-related proteins was decreased. TM combined with oxaliplatin enhanced the sensitivity of TE-1 cells to oxaliplatin. BEZ235 promoted the incidence of autophagy and apoptosis and elevated the sensitivity of TE-1 cells to oxaliplatin. Conclusion Taken together, TM induced ERS in EC cells and promoted autophagy and apoptosis, and increased the sensitivity of TE-1 to oxaliplatin through inhibiting AKT/mTOR signaling pathway.关键词
食管癌/内质网应激/自噬/凋亡/AKT/mTOR/TE-1细胞/奥沙利铂/化疗耐药Key words
Esophageal cancer/ Endoplasmic reticulum stress/ Autophagy/ Apoptosis/ AKT/mTOR pathway/ Oxaliplatin/ Chemotherapy resistance分类
医药卫生引用本文复制引用
SHEN Erdong,WENG Jie,WEN Fang,XIAO Jia,LUO Pan,XIE Wangti,SU Yuqi,HUANG Huiyun..衣霉素诱导的内质网应激对人食管癌细胞自噬和凋亡的影响及其与奥沙利铂化疗耐药的关系[J].肿瘤药学,2019,9(1):26-34,9.基金项目
基金项目:湖南省自然科学基金面上项目(2017JJ2260). （2017JJ2260）
