空军军医大学学报2024，Vol.45Issue(7)：756-762,7.DOI:10.13276/j.issn.2097-1656.2024.07.006
维甲酸介导的线粒体片段化抑制肝癌细胞营养缺乏相关凋亡抵抗
Retinoic acid-mediated mitochondrial fragmentation inhibits apoptosis resistance related to nutrient deficiency in hepatocellular carcinoma cells
摘要
Abstract
Objective To explore how metabolites and mitochondria regulate the survival of hepatocellular carcinoma(HCC)cells and its related mechanisms in a nutrient-deficient environment.Methods Transcriptomic data of sensitive and tolerant HCC samples treated by transarterial chemoembolization(TACE)were analyzed to identify the critical pathways for HCC cells to resist nutrient deficiency.The content of retinoic acid was detected in nutrient-deprived tolerant(HLF,Huh7)and sensitive(Hep3B,HLE)cells.HCC cells were treated with retinoic acid or retinoic acid receptor inhibitors.MTS assays and flow cytometry were used to detect the growth and apoptosis of the cells under nutrient deprivation.The influence of retinoic acid on the number and morphology of mitochondria in HCC cells was observed using transmission electron microscopy and laser scanning confocal microscopy.Results Transcriptomic analysis revealed that differentially expressed genes between TACE-treated tolerant and sensitive HCC tissues were predominantly enriched in retinol metabolism pathway.Furthermore,it was found that retinoic acid,a metabolite of retinol metabolism,was significantly reduced in tolerant HCC cells compared with sensitive HCC cells under nutrient-deprived conditions(P＜0.01).Supplementation of retinoic acid in HLF cells subjected to nutrient deprivation led to mitochondrial fragmentation and increased cell death(P＜0.01).In contrast,inhibition of retinoic acid receptor in Hep3B cells resulted in reduced mitochondrial fragmentation and decreased cell death(P＜0.01).Conclusion Supplementation of retinoic acid can inhibit the apoptosis resistance of HCC cells under nutrient-deficient conditions by inducing mitochondrial fragmentation,while low levels of retinoic acid can promote apoptosis resistance of HCC cells induced by nutrient deficiency by enhancing mitochondrial fusion.关键词
维甲酸/肝癌/线粒体片段化/营养剥夺Key words
retinoic acid/hepatocellular carcinoma/mitochondrial fragmentation/nutrient deprivation分类
医药卫生引用本文复制引用
杜钰璐,陈佳琪,高铭舒,李佳颖,廖达文,王星琛,张志刚,黄启超,季乐乐..维甲酸介导的线粒体片段化抑制肝癌细胞营养缺乏相关凋亡抵抗[J].空军军医大学学报,2024,45(7):756-762,7.基金项目
国家自然科学基金面上项目(81972590) （81972590）
