中医药基于表观遗传调控肝细胞癌的作用机制研究进展

Mechanism of Treatment of Hepatocellular Carcinoma with Traditional Chinese Medicine Based on Epigenetic Regulation:A Review

肝细胞癌(HCC)是目前全球第6大常见癌症。近年来,HCC的临床早期诊断及治疗方案不断改进和优化,但患者的预后情况仍不十分乐观,究其原因是其发生发展机制尚未完全阐明。因此,深入探讨HCC发生发展的分子机制和关键调控环节,对进一步提高我国肝癌的诊疗水平具有重要意义。表观遗传因其可逆性和易于调控的特点成为研究热点。根据相关研究表明,HCC在起始、促进和进展阶段涉及多种遗传和表观遗传变化的积累。根据中医药传统理论,中医将肝癌归于“疳积”“胁痛”“鼓胀”“癥瘕积聚”等范畴。中医药在治疗肝癌方面具有低不良反应、多靶点、多机制等特有优势,抑制肿瘤生长,改善患者的临床症状并提高其生存质量。中药及其活性成分通过表观遗传调控DNA甲基化、组蛋白修饰和非编码RNA等方面发挥抗肿瘤的作用,以发挥HCC治疗优势。表观遗传调控紊乱导致的基因表达异常参与HCC疾病的发生发展各个阶段。中医药基于表观遗传调控HCC的相关研究为数不多,在基础及临床实验上还有较大的发展空间。该文旨在综述表观遗传调控HCC发生发展作用机制并围绕相关机制开展的中医药实验研究成果进行归纳总结,以期为日后HCC的发生发展机制研究及中医药对HCC的临床诊疗提供理论依据。

Hepatocellular carcinoma(HCC)is the sixth most common cancer in the world.In recent years,the clinical early diagnosis and treatment protocols of HCC have been improved,whereas the prognosis of patients is still not satisfactory,which is due to the fact that the mechanism of HCC development has not been fully elucidated.Therefore,it is of great significance to explore the molecular mechanisms and key regulatory links of hepatocellular carcinoma development to further improve the diagnosis and treatment of HCC in China.Epigenetics has become a research hotspot because of its reversibility and easy regulation.According to relevant studies,HCC involves the accumulation of multiple genetic and epigenetic changes during the initiation,promotion,and progression stages.HCC is categorized as infantile malnutrition with accumulation,hypochondriac pain,tympan ites,and abdominal mass in traditional Chinese medicine(TCM).In the treatment of HCC,TCM with low toxicity,multi-targets,and multi-mechanisms can inhibit tumor growth,alleviate the clinical symptoms,and enhance the quality of life of the patients.Chinese medicines and their active ingredients exert anti-HCC effects through epigenetic regulation of DNA methylation,histone modification,and non-coding RNA.Abnormal gene expression due to epigenetic regulation disorders is involved in all stages of HCC development.There are few studies on epigenetic regulation in TCM treatment of HCC,and there is still much room for development in basic and clinical trials.This paper reviews the mechanism of epigenetic regulation in HCC and summarizes the experimental results of TCM research on the related mechanism,with a view to providing a theoretical basis for future research on the mechanism of HCC development and clinical diagnosis and treatment of hepatocellular carcinoma with TCM.