谷胱甘肽转运蛋白SLC25A39在肝癌细胞凋亡中的作用

doi:10.3969/j.issn.1004-616x.2026.01.006

癌变·畸变·突变 ›› 2026, Vol. 38 ›› Issue (1): 34-40,58.doi: 10.3969/j.issn.1004-616x.2026.01.006

• 论著 • 上一篇

谷胱甘肽转运蛋白SLC25A39在肝癌细胞凋亡中的作用

黄新怡^1,2,3, 白瑞萍², 花福增², 席浩博², 于卫华², 郑刚^1,3

1. 甘肃中医药大学公共卫生学院, 甘肃兰州 730000;
2. 空军军医大学军事预防医学系军事毒理学与防化医学教研室/陕西省自由基生物学与医学重点实验室, 陕西西安 710032;
3. 空军军医大学军事预防医学系劳动卫生与环境卫生学教研室/特殊作业环境危害评估与防治教育部重点实验室, 陕西西安 710032

收稿日期:2025-08-27 修回日期:2025-10-15 发布日期:2026-01-30
通讯作者: 于卫华, 郑刚
基金资助:
国家自然科学基金(32171231)

Role of glutathione transporter SLC25A39 in apoptosis of hepatoma cells

HUANG Xinyi^1,2,3, BAI Ruiping², HUA Fuzeng², XI Haobo², YU Weihua², ZHENG Gang^1,3

1. School of Public Health, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu;
2. Department of Military Toxicology and Chemical Defense Medicine, School of Military Preventive Medicine, Air Force Medical University/Key Laboratory of Free Radical Biology and Medicine of Shaanxi Province, Xi'an 710032;
3. Department of Occupational and Environmental Health, School of Military Preventive Medicine, Air Force Medical University/Key Laboratory of Environmental Hazard Assessment and Prevention of Special Operational Environment of Ministry of Education, Xi'an 710032, Shaanxi, China

Received:2025-08-27 Revised:2025-10-15 Published:2026-01-30

摘要/Abstract

摘要： 目的：探讨谷胱甘肽转运蛋白SLC25A39在调节肝癌细胞线粒体稳态和细胞凋亡中的作用。方法：通过HCCDB公共数据库，分析肝癌与癌旁组织中SLC25A39表达水平及其与肝癌患者生存期的关系。然后采用转染shSLC25A39慢病毒建立SLC25A39敲减HepG2细胞模型，实时荧光定量PCR (qPCR)和Western blot法验证敲减效率。通过检测SLC25A39敲减细胞在不同时段的增殖活力，探究SLC25A39表达对肝癌细胞的影响。选用50 μmol/L叔丁基过氧化氢(TBHP)处理HepG2细胞12 h诱导细胞凋亡模型，分别采用CCK-8法检测细胞活力变化，Annexin V/PI双染法检测细胞凋亡。此外，采用MitoRT染色和提纯线粒体法检测线粒体中GSH含量；JC-1染色法检测线粒体膜电位；MitoSOX染色法检测线粒体活性氧(ROS)水平；生物荧光法检测细胞内ATP水平。结果：肝癌公共库数据分析表明，肝癌组织中SLC25A39表达较癌旁组织升高(P<0.05)，且与患者不良预后密切相关。qPCR和Western blot法检测结果显示SLC25A39敲减细胞中SLC25A39 mRNA和蛋白表达均较对照组明显下降(P<0.05)，表明SLC25A39敲减HepG2细胞模型构建成功。检测0~96 h细胞数量结果显示，与对照组相比，SLC25A39敲减细胞增殖速度明显减慢，且随培养时间延长两组存活细胞数量差异逐渐增大(P<0.05)。使用TBHP刺激引起细胞氧化损伤后发现，与空载对照组相比，SLC25A39敲减组细胞活力明显下降(P<0.05)；且细胞线粒体中GSH水平和膜电位、细胞内ATP含量均下降，同时细胞凋亡率、线粒体ROS水平升高(均为P<0.05)，提示SLC25A39敲减使线粒体氧化应激和功能损伤加重(P<0.05)。结论：抑制肝癌细胞中SLC25A39高表达介导的线粒体GSH摄取可促进肝癌细胞的凋亡，靶向抑制SLC25A39有望为肝癌治疗提供新思路。

关键词: SLC25A39, 肝癌细胞, 抗凋亡, 谷胱甘肽, 线粒体稳态

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.

Key words: SLC25A39, hepatoma cells, anti-apoptosis, glutathione, mitochondrial homeostasis

中图分类号:

R735.7

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.

HUANG Xinyi, BAI Ruiping, HUA Fuzeng, XI Haobo, YU Weihua, ZHENG Gang. Role of glutathione transporter SLC25A39 in apoptosis of hepatoma cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2026, 38(1): 34-40,58.

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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

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