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

Abstract

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

CLC Number:

R735.7

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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Role of glutathione transporter SLC25A39 in apoptosis of hepatoma cells

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