低氧在Erastin诱导的胰腺导管腺癌细胞铁死亡中的作用及其机制  

The role and mechanism of hypoxia in Erastin-induced ferroptosis of pancreatic ductal adenocarcinoma cells

作　　者：高钦玥 宋廉[1] 吴琪炜 魏士杰 刘赛 龚爱华[2] 朱海涛[1] 王冬青[1] GAO Qinyue;SONG Lian;Wu Qiwei;WEI Shijie;LIU Sai;GONG Aihua;ZHU Haitao;WANG Dongqing(Department of Radiology,Affiliated Hospital of Jiangsu University,Jiangsu Province,Zhenjiang 212000,China;School of Medicine,Jiangsu University,Jiangsu Province,Zhenjiang 212000,China)

机构地区：[1]江苏大学附属医院影像科,江苏镇江212000 [2]江苏大学医学院,江苏镇江212000

出　　处：《中国医药导报》2021年第18期22-25,39,共5页China Medical Herald

基　　金：江苏省自然科学基金资助项目(BK20191223);江苏省卫生厅重点项目(K2019024);中华国际医学交流基金会SKY影像科研项目(Z-2014-07-1912-17)。

摘　　要：目的研究低氧在Erastin诱导的胰腺导管腺癌(PDAC)细胞铁死亡中的作用及机制。方法PDAC细胞分为四组,常氧DMSO组、常氧Erastin组(5.0μmol/L Erastin溶液)、低氧DMSO组、低氧Erastin组(5.0μmol/L Erastin溶液)。孵育72 h用CCK-8法检测细胞活性;全波长酶标仪检测还原型谷胱甘肽(GSH)和丙二醛(MDA)含量;RT-qPCR检测去乙酰酶Sirtuin3(SIRT3)的mRNA的表达水平;动物皮下成瘤实验检测体内低氧对铁死亡影响。结果低氧Erastin组PANC1细胞活性,还原型GSH相对含量,SIRT3的mRNA相对表达水平均高于常氧Erastin组,差异有统计学意义(P<0.05)。低氧Erastin组MDA相对含量低于常氧Erastin组(P<0.05)。常氧Erastin组的肿瘤体积小于常氧DMSO组,差异有统计学意义(P<0.05)。低氧Erastin组肿瘤体积与低氧DMSO组比较,差异无统计学意义(P>0.05)。结论低氧抑制Erastin诱导的PDAC细胞铁死亡,SIRT3表达水平增高是其机制之一。Objective To study the role and mechanism of hypoxia in Erastin-induced iron death of pancreatic ductal adeno carcinoma(PDAC)cells.Methods PDAC cells were divided into four groups,normoxia DMSO group,normoxia Erastin group(5.0μmol/L Erastin solution),hypoxia DMSO group,and hypoxia Erastin group(5.0μmol/L Erastin solution).After 72 hours of incubation,the cell activity was detected by CCK-8 method;full-wavelength microplate reader detects the content of reduced glutathione(GSH)and malondialdehyde(MDA);RT-qPCR detected the expression level of the deacetylase Sirtuin3(SIRT3)mRNA;animal subcutaneous tumor formation experiments were used to detect the effects of hypoxia on iron death in vivo.Results The PANC1 cell activity,the relative content of reduced GSH,and the relative expression of SIRT3 mRNA in the hypoxic Erastin group were higher than those of the normoxic Erastin group,and the differences were statistically significant(P<0.05).The relative content of MDA in the hypoxic Erastin group was lower than that of the normoxic Erastin group(P<0.05).The tumor volume of the normoxic Erastin group was smaller than that of the normoxic DMSO group,and the difference was statistically significant(P<0.05).There was no significant difference in tumor volume between the hypoxic Erastin group and the hypoxic DMSO group(P>0.05).Conclusion Hypoxia inhibits the iron death of PDAC induced by Erastin,and the increased expression of SIRT3 is one of its mechanisms.

关 键 词：胰腺导管腺癌 低氧 Erastin 铁死亡 Sirtuin3 

分 类 号：R735.34[医药卫生—肿瘤]