文章：

LFHP-1c 在体外独立于 PGAM5 抑制肝细胞癌的细胞活力

LFHP-1c Attenuates Hepatocellular Carcinoma Viability In Vitro Independent of PGAM5

原文发布日期：6 May 2025

DOI: 10.3390/cancers17091573

类型: Article

开放获取: 是

英文摘要：

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. Methods: 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. Results: 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 andPGAM5knockout cell lines following LFHP-1c exposure. Cell viability was reduced following LFHP-1c treatment inPGAM5knockout cell lines. Conclusions: LFHP-1c reduces hepatoma and HCC viability and enhances ROS production, but these effects are independent of PGAM5.

摘要翻译： 

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可抑制HCC生长。近期，一种新型PGAM5小分子抑制剂LFHP-1c的特性已被阐明。本研究旨在探究LFHP-1c在细胞模型中是否能有效降低HCC的存活能力。方法：分别用LFHP-1c处理肝癌细胞系HepG2和HCC细胞系HuH7。采用无标记成像技术量化细胞生长情况。通过发光或荧光检测法测定细胞活力及活性氧（ROS）生成水平。利用免疫印迹法检测抗氧化及代谢相关蛋白的表达。以HepG2和HuH7的PGAM5敲除细胞系作为阴性对照。结果：LFHP-1c处理可抑制HepG2和HuH7细胞系的生长并降低其活力。在野生型及PGAM5敲除细胞系中，LFHP-1c暴露均能上调ROS生成。PGAM5敲除细胞系经LFHP-1c处理后细胞活力亦出现下降。结论：LFHP-1c能够降低肝癌及HCC细胞活力并促进ROS生成，但这些效应不依赖于PGAM5。

原文链接：

LFHP-1c Attenuates Hepatocellular Carcinoma Viability In Vitro Independent of PGAM5