Muthusamy Ganesan, Liu Chin-Chi, Johnston Andrea N
School of Veterinary Medicine, Veterinary Clinical Sciences, Louisiana State University, Baton Rouge, LA 70802, USA.
School of Veterinary Medicine, Office of Research and Graduate Education, Louisiana State University, Baton Rouge, LA 70802, USA.
Cancers (Basel). 2025 May 6;17(9):1573. doi: 10.3390/cancers17091573.
BACKGROUND/OBJECTIVES: Upregulation of phosphoglycerate mutase 5 (PGAM5) is correlated with reduced survival outcomes in hepatocellular carcinoma (HCC). PGAM5 knockdown or knockout attenuates HCC growth in in vitro and in vivo models. A novel small molecule inhibitor of PGAM5, LFHP-1c, has recently been characterized. The objective of this study was to determine if LFHP-1c effectively reduces HCC viability in cell models.
The hepatoma and HCC cell lines, HepG2 and HuH7, respectively, were treated with LFHP-1c. Label-free imaging was used to quantify growth. Cellular viability and reactive oxygen species (ROS) production were measured using luminescent or fluorescent assays. Expression of antioxidant and metabolic proteins was measured by immunoblot. HepG2 and HuH7 PGAM5 knockout cell lines were used as negative controls.
Treatment with LFHP-1c reduced cell growth and viability in HepG2 and HuH7 cell lines. Reactive oxygen species production was upregulated in both wild-type and knockout cell lines following LFHP-1c exposure. Cell viability was reduced following LFHP-1c treatment in knockout cell lines.
LFHP-1c reduces hepatoma and HCC viability and enhances ROS production, but these effects are independent of PGAM5.
背景/目的：磷酸甘油酸变位酶5（PGAM5）的上调与肝细胞癌（HCC）患者生存率降低相关。在体外和体内模型中，敲低或敲除PGAM5可减弱HCC的生长。最近已鉴定出一种新型的PGAM5小分子抑制剂LFHP-1c。本研究的目的是确定LFHP-1c是否能有效降低细胞模型中HCC的活力。
分别用LFHP-1c处理肝癌细胞系HepG2和HCC细胞系HuH7。采用无标记成像定量细胞生长。使用发光或荧光测定法测量细胞活力和活性氧（ROS）生成。通过免疫印迹法检测抗氧化和代谢蛋白的表达。将HepG2和HuH7 PGAM5敲除细胞系用作阴性对照。
LFHP-1c处理可降低HepG2和HuH7细胞系的细胞生长和活力。LFHP-1c处理后，野生型和敲除细胞系中的ROS生成均上调。LFHP-1c处理后，敲除细胞系中的细胞活力降低。
LFHP-1c可降低肝癌和HCC的活力并增强ROS生成，但这些作用与PGAM5无关。
