Research Progress of Warburg Effect in Hepatocellular Carcinoma

Yanguang Yang, Yuting Gao, Yajun Xiong, Yi Gong, Junlan Lu, Yuman Zhang, Dan Wang, Zhihan Liu, Xinli Shi
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Abstract

The Warburg effect, also called aerobic glycolysis, refers to tumor cells that metabolize glucose through glycolysis even in the presence of oxygen. This rapid breakdown of glucose fuels the fast development, growth, and migration of tumor cells. Lactate, the final product of aerobic glycolysis, contributes to an acidic environment within the tumor, promoting the formation of an immunosuppressive microenvironment and accelerating tumor progression by impeding anti-tumor immunity. Numerous studies have confirmed the critical role of aerobic glycolysis in the occurrence and development of hepatocellular carcinoma by influencing tumor cells proliferation, invasion, metastasis, apoptosis, immune escape, angiogenesis, and more. Clinical trials have shown that inhibitors of rate-limiting enzymes in the glycolysis pathway can enhance the effectiveness of sorafenib, a targeted drug for hepatocellular carcinoma, by reducing drug resistance. Additionally, active components of traditional Chinese medicine and specific compound prescriptions are gaining attention for their potential to target and regulate aerobic glycolysis in hepatocellular carcinoma. Therefore, inhibiting the aerobic glycolysis pathway holds promise as a therapeutic strategy for treating liver tumors. This manuscript aims to review the role, research directions, and clinical studies of aerobic glycolysis in hepatocellular carcinoma.
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肝细胞癌中的沃伯格效应研究进展
沃伯格效应又称有氧糖酵解,是指肿瘤细胞即使在有氧的情况下也能通过糖酵解代谢葡萄糖。葡萄糖的快速分解为肿瘤细胞的快速发育、生长和迁移提供了燃料。乳酸是有氧糖酵解的最终产物,会使肿瘤内形成酸性环境,促进免疫抑制微环境的形成,并通过阻碍抗肿瘤免疫加速肿瘤的进展。大量研究证实,有氧糖酵解通过影响肿瘤细胞的增殖、侵袭、转移、凋亡、免疫逃逸、血管生成等,在肝细胞癌的发生和发展中起着关键作用。临床试验表明,糖酵解途径中限速酶的抑制剂可以通过减少耐药性来提高肝癌靶向药物索拉非尼的疗效。此外,传统中药和特定复方中的活性成分也因其靶向调节肝细胞癌中有氧糖酵解的潜力而备受关注。因此,抑制有氧糖酵解途径有望成为治疗肝脏肿瘤的一种治疗策略。本手稿旨在回顾有氧糖酵解在肝细胞癌中的作用、研究方向和临床研究。
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