癌变·畸变·突变2026,Vol.38Issue(1):34-40,58,8.DOI:10.3969/j.issn.1004-616x.2026.01.006
谷胱甘肽转运蛋白SLC25A39在肝癌细胞凋亡中的作用
Role of glutathione transporter SLC25A39 in apoptosis of hepatoma cells
摘要
Abstract
OBJECTIVE:To investigate the role of the mitochondrial glutathione(GSH)transporter SLC25A39 in regulating mitochondrial homeostasis and apoptosis in hepatoma cells.METHODS:Data on expression of SLC25A39 in tumor and adjacent tissues and its relationship with the survival time of hepatocellular carcinoma patients were obtained using the HCCDB public database.SLC25A39-knockdown HepG2 cells were verified by real-time quantitative PCR(qPCR)and Western blot.Impact of SLC25A39 expression on the proliferation of liver cancer cells was investigated using the CCK-8 method.HepG2 cells were treated with 50 μmol/L tert-butyl hydroperoxide(TBHP)for 12 hours to induce cell apoptosis.Cell viability was assessed using the CCK-8 assay,and cell apoptosis rates were detected by Annexin V/PI method.In addition,mitochondrial GSH content was detected by MitoRT staining and purified mitochondrial methods.Mitochondrial membrane potential was detected by JC-1 staining.Mitochondrial reactive oxygen species(ROS)levels were detected by MitoSOX staining.Intracellular ATP levels were detected by bioluminescence assay.RESULTS:Results from the HCCDB public database indicate that levels of SLC25A39 in most hepatocellular carcinomas were higher than those in their adjacent tissues(P<0.05).Expression of SLC25A39 was positively correlated with poor prognosis in cancer patients.Compared to the control cells,the proliferation rate of SLC25A39 knockdown cells gradually decreased,and the apoptosis ratio significantly increased(all P<0.05).Compared to the control cells,knockdown of SLC25A39 in HepG2 cells resulted in decreased mitochondrial GSH,mitochondrial membrane potential,and cellular ATP content,while mitochondrial ROS levels were increased(all P<0.05).After stimulation with TBHP,the apoptosis rate in SLC25A39 knockdown cells significantly increased compared to the control group,and both mitochondrial oxidative stress and functional impairment were further exacerbated(P<0.05).CONCLUSION:SLC25A39 was capable of promoting hepatocellular carcinoma cells to maintain mitochondrial homeostasis and redox balance by enhancing mitochondrial GSH uptake capacity,thereby conferring enhanced anti-apoptotic and survival capabilities.Targeted inhibition of SLC25A39 may be useful for the treatment of hepatocellular carcinoma.关键词
SLC25A39/肝癌细胞/抗凋亡/谷胱甘肽/线粒体稳态Key words
SLC25A39/hepatoma cells/anti-apoptosis/glutathione/mitochondrial homeostasis分类
医药卫生引用本文复制引用
黄新怡,白瑞萍,花福增,席浩博,于卫华,郑刚..谷胱甘肽转运蛋白SLC25A39在肝癌细胞凋亡中的作用[J].癌变·畸变·突变,2026,38(1):34-40,58,8.基金项目
国家自然科学基金(32171231) (32171231)