Targeting Glycolytic Enzymes with 3-Bromopyruvic Acid to Enhance the Efficacy of Interventional Embolization in Hepatocellular Carcinoma

Abstract

Objective

Tumour cells in a hypoxic state are more invasive, have stronger self-renewal capabilities, and are difficult to treat because of their ability to promote tumour recurrence and metastasis. The glycolysis inhibitor 3-bromopyruvic acid (3-BrPA) can completely inactivate glycolytic enzymes at extremely low drug concentrations, thereby exerting a strong inhibitory effect on the glucose energy metabolism of tumor cells. Therefore, we tested the inhibitory effect of 3-BrPA on hepatocellular carcinoma cells (HepG2) in vitro; then, we used the VX2 liver cancer model to study the antitumour effect of 3-BrPA combined with interventional embolization on liver cancer.

Methods

In vitro, a CCK-8 assay was used to detect the inhibitory effect of different concentrations of 3-BrPA on HepG2 cells, and light microscopy confirmed that the HepG2 cells were completely dead. Western blotting was used to detect the expression of key proteins involved in apoptosis. A total of 30 New Zealand white rabbits were used to establish a liver cancer model and were randomly divided into 3 groups 2 weeks after tumor establishment: the control group was perfused with saline in the hepatic artery; the transcatheter arterial embolization (TAE) group was given TAE; and the experimental group was perfused with 3-BrPA combined with TAE. The tumor-bearing rabbits were killed one week after surgery. The tumor volume and tumor necrosis ratio were calculated via the histopathological examination.

Results

In vitro, the inhibitory effect of 3-BrPA on HepG2 cells increased with increasing concentration. 3-BrPA (100 μmol/L) could induce the necrosis of HepG2 cells. Stimulation with 50 μmol/L 3-BrPA could activate the tumor cell apoptosis pathway. 3-BrPA combined with TAE treatment could significantly inhibit tumor growth and cause more complete tumor necrosis.

Conclusion3-BrPA not only has antitumour effects in vitro but can also significantly improve antitumour effects in the hypoxic microenvironment after embolization in vivo.

Keywords

Hepatocellular carcinoma / Glycolysis inhibitor / 3-Bromopyruvic acid / Interventional embolization / Anticancer effects / Tumor necrosis

© The Author(s), under exclusive licence to Huazhong University of Science and Technology 2025

Acknowledgements The authors thank to National Natural Science Foundation of China (No. 82202281) for the funding support, and Yu- miao Wei for his review of the manuscript.

Authors Contributions All authors contributed to this study. Min Wang and Xiao-ning Wu conceived and designed the experiments, analysed and interpreted the data, and contributed to writing the manuscript. Xu Cheng conducted cell experiments (including cell culture, CCK-8 assay, observation under light microscopy, and Western blot detection). Xiao-peng Guo and Song-lin Song conducted animal experiments (including rabbit breeding, liver cancer model establishment, CT examination, DSA, animal specimen acquisition, and HE staining), provided logistical and administrative support and ensured compliance with ethical standards. Zhuang-lin Zeng and Ai-ping Cheng contributed to reviewing literature, providing intellectual input, and approving the final version of the manuscript.

Data Availability The data that support the findings of the current study are available from the corresponding author on reasonable request. Please contact E-mail: [e-mail] or [e-mail].

Declarations

Ethical Approval and Consent to Participate All animal experiments were approved by the Experimental Animal Ethics Committee of Huazhong University of Science and Technology (IACUC Approval Number: 2455).

Human and Animal Rights Not applicable.

Consent for Publication This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. All authors have approved the manuscript and agreed to submit it for publication in Current Medical Science.

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