Department of Medical Technology, Kagawa Prefectural University of Health Sciences, 281-1, Hara, Mure-cho, Takamatsu 761-0123, Kagawa, Japan.
Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe, Miki-cho 761-0793, Kagawa, Japan.
Nutrients. 2024 Feb 6;16(4):472. doi: 10.3390/nu16040472.
Numerous nutritional factors increase the risk of hepatocellular carcinoma (HCC) development. The dysregulation of zinc, copper, and selenium homeostasis is associated with the occurrence of HCC. The impairment of the homeostasis of these essential trace elements results in oxidative stress, DNA damage, cell cycle progression, and angiogenesis, finally leading to hepatocarcinogenesis. These essential trace elements can affect the microenvironment in HCC. The carrier proteins for zinc and copper and selenium-containing enzymes play important roles in the prevention or progression of HCC. These trace elements enhance or alleviate the chemosensitivity of anticancer agents in patients with HCC. The zinc, copper, or selenium may affect the homeostasis of other trace elements with each other. Novel types of cell death including ferropotosis and cupropotosis are also associated with hepatocarcinogenesis. Therapeutic strategies for HCC that target these carrier proteins for zinc and copper or selenium-containing enzymes have been developed in in vitro and in vivo studies. The use of zinc-, copper- or selenium-nanoparticles has been considered as novel therapeutic agents for HCC. These results indicate that zinc, copper, and selenium may become promising therapeutic targets in patients with HCC. The clinical application of these agents is an urgent unmet requirement. This review article highlights the correlation between the dysregulation of the homeostasis of these essential trace elements and the development of HCC and summarizes the current trends on the roles of these essential trace elements in the pathogenesis of hepatocarcinogenesis.
许多营养因素会增加肝细胞癌（HCC）发生的风险。锌、铜和硒稳态的失调与 HCC 的发生有关。这些必需微量元素稳态的损害导致氧化应激、DNA 损伤、细胞周期进展和血管生成，最终导致肝癌发生。这些必需微量元素可以影响 HCC 的微环境。锌和铜的载体蛋白以及含硒酶在 HCC 的预防或进展中发挥重要作用。这些微量元素可增强或减轻 HCC 患者抗癌药物的化疗敏感性。锌、铜或硒可能会相互影响其他微量元素的稳态。新型细胞死亡类型，包括铁死亡和铜死亡，也与肝癌发生有关。针对锌和铜载体蛋白或含硒酶的 HCC 治疗策略已在体外和体内研究中得到开发。锌、铜或硒纳米颗粒的应用被认为是 HCC 的新型治疗剂。这些结果表明，锌、铜和硒可能成为 HCC 患者有前途的治疗靶点。这些药物的临床应用是一个迫切需要满足的需求。本文综述了这些必需微量元素稳态失调与 HCC 发生之间的相关性，并总结了这些必需微量元素在肝癌发生发病机制中的作用的最新趋势。
