PDF(Pubmed)
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.
摘要：
经动脉化疗栓塞术(TACE)可延长肝细胞癌(HCC)患者的生存期;由于不完全栓塞率高，其疗效有限。栓塞后缺氧可引起肿瘤微环境的一系列改变,包括乳酸脱氢酶A(LDHA)上调。因此,本研究评估了LDHA抑制剂的抗肿瘤作用和潜在机制，草甲酸钠（Ox），结合TACE，采用兔VX2肝脏肿瘤模型。在兔的左肝叶中创建VX2肝肿瘤模型，经过14天的治疗，处死兔子以收集肿瘤组织和血液样品。Ox的抗肿瘤作用,以及Ox和TACE的结合，并通过组织病理学评估评估治疗后肿瘤微环境的变化，并通过测量血清丙氨酸氨基转移酶水平的变化来分析治疗的安全性，天冬氨酸转氨酶,血尿素氮和肌酐。结果表明，与其他组相比，Ox和TACE的组合显着改善了抗肿瘤作用。因为它显著抑制肿瘤生长。此外,Ox+TACE治疗下调血管内皮生长因子和基质金属蛋白酶-9，增强CD3+和CD8+T细胞向肿瘤组织的浸润，因此表明OxTACE可能对增加肿瘤微环境中免疫细胞的浸润具有协同作用。具有良好的耐受性和可控制的肝肾功能损害，靶向代谢重编程可以促进TACE的疗效，从而为未来晚期HCC患者的临床治疗提供了新的途径。
