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AMPK会成为肝细胞癌的潜在治疗靶点吗?

Will AMPK be a potential therapeutic target for hepatocellular carcinoma?

作者信息

Chen Guo, Li Ming-Yuan, Yang Jing-Yi, Zhou Zhen-Hua

机构信息

Department of Oncology, Anhui Hospital, Shuguang Hospital, Affiliated to Shanghai University of Traditional Chinese Medicine Hefei, Anhui, China.

Department of Oncology, Feixi Hospital of Traditional Chinese Medicine Feixi, Hefei, Anhui, China.

出版信息

Am J Cancer Res. 2024 Jul 15;14(7):3241-3258. doi: 10.62347/YAVK1315. eCollection 2024.

DOI:10.62347/YAVK1315
PMID:39113872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11301289/
Abstract

Cancer is the disease that poses the greatest threat to human health today. Among them, hepatocellular carcinoma (HCC) is particularly prominent due to its high recurrence rate and extremely low five-year postoperative survival rate. In addition to surgical treatment, radiotherapy, chemotherapy, and immunotherapy are the main methods for treating HCC. Due to the natural drug resistance of chemoradiotherapy and targeted drugs, satisfactory results have not been achieved in terms of therapeutic efficacy and cost. AMP-Activated Protein Kinase (AMPK) is a serine/threonine protein kinase. It mainly coordinates the metabolism and transformation of energy between cells, which maintaining a balance between energy supply and demand. The processes of cell growth, proliferation, autophagy, and survival all involve various reaction of cells to energy changes. The regulatory role of AMPK in cellular energy metabolism plays an important role in the occurrence, development, treatment, and prognosis of HCC. Here, we reviewed the latest progress on the regulatory role of AMPK in the occurrence and development of HCC. Firstly, the molecular structure and activation mechanism of AMPK were introduced. Secondly, the emerging regulator related to AMPK and tumors were elaborated. Next, the multitasking roles of AMPK in the occurrence and development mechanism of HCC were discussed separately. Finally, the translational implications and the challenges of AMPK-targeted therapies for HCC treatment were elaborated. In summary, these pieces of information suggest that AMPK can serve as a promising specific therapeutic target for the treatment of HCC.

摘要

癌症是当今对人类健康构成最大威胁的疾病。其中,肝细胞癌(HCC)因其高复发率和极低的术后五年生存率而尤为突出。除手术治疗外,放疗、化疗和免疫疗法是治疗HCC的主要方法。由于放化疗和靶向药物存在天然耐药性,在治疗效果和成本方面尚未取得令人满意的结果。AMP激活蛋白激酶(AMPK)是一种丝氨酸/苏氨酸蛋白激酶。它主要协调细胞间能量的代谢与转换,维持能量供需平衡。细胞生长、增殖、自噬和存活过程均涉及细胞对能量变化的各种反应。AMPK在细胞能量代谢中的调节作用在HCC的发生、发展、治疗及预后中发挥着重要作用。在此,我们综述了AMPK在HCC发生发展中调节作用的最新进展。首先,介绍了AMPK的分子结构和激活机制。其次,阐述了与AMPK和肿瘤相关的新兴调节因子。接下来,分别讨论了AMPK在HCC发生发展机制中的多重作用。最后,阐述了AMPK靶向治疗HCC的转化意义及面临的挑战。综上所述,这些信息表明AMPK有望成为治疗HCC的特异性治疗靶点。