目的 研究肝星状细胞(HSCs)在肝细胞癌(HCC)中的代谢调控和凋亡机制。 方法 对基因表达综合数据库(GEO) 中 GSE25097 进行分析,确定在肝硬化及肝癌患者中 HSCs 表达变化。 选取代表 HSCs 的 LX2 细胞系与代表 HCC 的 HepG2 细 胞系进行体外实验。 Transwell 共培养 LX2 与 HepG2 细胞为实验组,HepG2 单独培养为对照组,培养 3 d 后二代测序。 通过生 物信息学结合流式细胞术探究 HSCs 对 HCC 的作用机制。 结果 GSE25097 分析结果显示肝硬化患者中 HSCs 表达量显著增加 (P<0. 05);与肝硬化患者相比,HCC 患者中 HSCs 表达量显著降低(P<0. 05)。 二代测序结果显示,两组差异基因主要涉及代 谢和凋亡。 代谢相关显著差异基因主要富集在代谢通路和 AMPK 信号通路,关键基因包括 SLC11A1、GPX3、PFKP 等。 凋亡相 关显著差异基因主要富集在肿瘤发病途径和肿瘤坏死因子(TNF)信号通路,关键基因包括 PDGFB、IGFBP3、FOS、DUSP1。 表 型实验证明 LX2 能够抑制 HepG2 增殖(P<0. 05)并促进 HepG2 的凋亡(P<0. 05,P<0. 01);线粒体膜电位实验也证实 LX2 能 够促进 HepG2 的凋亡(P<0. 01)。 结论 HSCs 对 HCC 具有直接抑制作用。 这一作用主要通过干扰肿瘤细胞代谢和促进凋亡 来实现。

Objective To investigate the role of hepatic stellate cells HSCs in hepatocellular carcinoma HCC . Method The study analyzed data from the GEO database GSE25097 to identify changes in HSCs expression in patients with liver cirrhosis and HCC. The LX2 cell line representing HSCs and the HepG2 cell line representing HCC were selected for in vitro experiments. The experimental group involved Transwell co-culture while the control group consisted of HepG2 cells cultured alone. After three days of culture second - generation sequencing was performed. The mechanism of HSCs ' effect on HCC was further explored using bioinformatics and flow cytometry. Result Analysis of GSE25097 data revealed a significant increase in HSCs expression in patients with liver cirrhosis P<0. 05 while a significant decrease was observed in HCC patients compared to those with cirrhosis P<0. 05 . Sequencing results indicated that the differentially expressed genes between the two groups were primarily involved in metabolism and apoptosis. Metabolism - related significantly different genes were mainly enriched in metabolic pathways and the AMPK signaling pathway with key genes including SLC11A1 GPX3 and PFKP. Apoptosis -related significantly different genes were enriched in cancer pathways and the TNF signaling pathway with key genes including PDGFB IGFBP3 FOS and DUSP1. Phenotypic experiments demonstrated that LX2 could inhibit HepG2 proliferation P<0. 05 and promote HepG2 apoptosis P<0. 05 P<0. 01 . Mitochondrial membrane potential experiments also confirmed that LX2 could promote HepG2 apoptosis P<0. 01 . Conclusion HSCs exert a direct inhibitory effect on HCC primarily by disrupting tumor cell metabolism and promoting apoptosis.