Targeting metabolic reprogramming promotes the efficacy of transarterial chemoembolization in the rabbit VX2 liver tumor model

Luo,Yi; Yang,Yong; Ye,Meize; Zuo,Jing

doi:10.3892/ol.2024.14244

Targeting metabolic reprogramming promotes the efficacy of transarterial chemoembolization in the rabbit VX2 liver tumor model

Authors:
- Yi Luo
- Yong Yang
- Meize Ye
- Jing Zuo
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Affiliations: Department of Interventional Radiology, The Second Hospital of Wuhan Iron and Steel (Group) Corp., Wuhan, Hubei 430022, P.R. China, Department of Oncology, The Second Hospital of Wuhan Iron and Steel (Group) Corp., Wuhan, Hubei 430022, P.R. China, Department of Interventional Radiology, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
Published online on: January 22, 2024 https://doi.org/10.3892/ol.2024.14244
Article Number: 111
Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transarterial chemoembolization (TACE) may prolong the survival of patients with hepatocellular carcinoma (HCC); however, its efficacy is limited due to the high rate of incomplete embolization. Hypoxia after embolization can cause a series of changes in the tumor microenvironment, including lactate dehydrogenase A (LDHA) upregulation. Therefore, the current study assessed the antitumor effect and the underlying mechanism of the LDHA inhibitor, sodium oxamate (Ox), combined with TACE, using the rabbit VX2 liver tumor model. VX2 liver tumor models were created in the left liver lobe of rabbits, and after 14 days of treatments, the rabbits were sacrificed for the collection of the tumor tissues and blood samples. The antitumor effects of Ox, and the combination of Ox and TACE, and changes in the tumor microenvironment after treatments were assessed by histopathological evaluation, and the safety of the treatments was analyzed by measuring changes in the serum levels of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine. The results demonstrated that the combination of Ox and TACE notably improved antitumor effects compared with in the other groups, as it significantly inhibited tumor growth. Additionally, treatment with Ox + TACE downregulated vascular endothelial growth factor and matrix metalloproteinase‑9, and enhanced the infiltration of CD3+ and CD8+ T cells into tumor tissues, thus suggesting that Ox + TACE may have a synergistic effect on increasing the infiltration of immune cells in the tumor microenvironment. With a well‑tolerated and manageable impairment of hepatorenal function, targeting metabolic reprogramming could promote the efficacy of TACE, thus providing novel avenues for the future clinical management of patients with advanced HCC.

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