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The role and mechanism of hypoxia in Erastin-induced ferroptosis of pancreatic ductal adenocarcinoma cells |
GAO Qinyue1 SONG Lian1 Wu Qiwei1 WEI Shijie1 LIU Sai1 GONG Aihua2 ZHU Haitao1 WANG Dongqing1 |
1.Department of Radiology, Affiliated Hospital of Jiangsu University, Jiangsu Province, Zhenjiang 212000, China;
2.School of Medicine, Jiangsu University, Jiangsu Province, Zhenjiang 212000, China |
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Abstract 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 (5.0 μmol/L Erastin solution), hypoxia DMSO group, and hypoxia Erastin group (5.0 μmol/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.
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