硫利达嗪诱导人肺鳞癌细胞SK-MES-1发生免疫原性死亡的机制研究  

Mechanism of immunogenic cell death of human pulmonary squamous cell carcinoma cells SK-MES-1 induced by thioridazine

作　　者：柯章敏 张玮 朱文艳 文昱婷 王丽 杨旸 朱颖 张秀伟 Ke Zhangmin;Zhang Wei;Zhu Wenyan;Wen Yuting;Wang Li;Yang Yang;Zhu Ying;Zhang Xiuwei(Department of Respiratory Medicine,Jiangning Hospital affiliated to Nanjing Medical University,Nanjing 211100,China)

机构地区：[1]南京医科大学附属江宁医院呼吸科,211100

出　　处：《国际呼吸杂志》2018年第22期1689-1693,共5页International Journal of Respiration

摘　　要：目的 探讨硫利达嗪是否诱导人肺鳞癌细胞SK-M ES-1发生免疫原性死亡并探讨其可能机制.方法 取处对数生长期的肺鳞癌细胞SK-MES-1,MTT法检测细胞增殖率,流式细胞术检测细胞膜上钙网蛋白表达率及细胞凋亡率,酶联免疫吸附试验法检测细胞上清中高迁移率族蛋白B1的含量,Western blot法检测内质网应激相关蛋白GRP78、CHOP表达水平.结果 硫利达嗪对SK-M ES-1细胞有显著的增殖抑制及促凋亡作用,且呈浓度依赖性.经硫利达嗪处理后内质网应激相关蛋白GRP78、CHOP上调,与对照组比较,差异有统计学意义(P值均<0.01),同时诱导SK-MES-1细胞内质网中钙网蛋白转移到细胞表面,促进高迁移率族蛋白B1分泌,与对照组比较,差异有统计学意义(P<0.01).结论 硫利达嗪可诱导人肺癌SK-MES-1细胞免疫原性死亡,其机制可能与诱导内质网应激及Caspase内外源性凋亡途径有关.Objective To investigate whether thialidazine induces immunogenic death of human pulmonary squamous cell carcinoma cells SK-M ES-1 and its possible mechanism .Methods SK-M ES-1 cells in logarithmic growth phase were taken to detect the cell proliferation rate by MTT ,the expression of calreticulin and apoptotic rate by flow cytometry ,the content of high mobility group protein B 1 in cell supernatant by enzyme linked immunosorbent assay ,and the expression levels of GRP 78 and CHOP by Western blot .Results Thioridazine could inhibit proliferation and promote apoptosis of SK-MES-1 cells in a concentration-dependent manner .Endoplasmic reticulum stress-related proteins GRP78 and CHOP were up-regulated after treatment with thiridazine ,and there was significant difference between the experimental group and the control group (all P <0 .01) .Calreticulin in SK-MES-1 cells was also induced to transfer to the cell surface .The secretion of high mobility group protein B 1 was increased ,and there was significant difference between the experimental group and the control group ( P < 0 .01 ) . Conclusions Thiodazide can induce the immunogenic death of human lung cancer SK-MES-1 cells , which may be related to the endoplasmic reticulum stress and the endogenous and exogenous apoptotic pathways of Caspase .

关 键 词：硫利达嗪 免疫原性死亡 内质网应激 肺鳞癌 

分 类 号：R734.2[医药卫生—肿瘤]