Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.

中文翻译：

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表没食子儿茶素没食子酸酯诱导肝星状细胞衰老并减弱肝细胞癌的发展

肝细胞癌 (HCC) 是一种高度病态的疾病，缺乏有效的治疗选择。HCC 源于慢性发炎和受损的肝组织；因此，化学预防可能是降低 HCC 发病率的有用策略。一些报道表明，从绿茶中提取的表没食子儿茶素没食子酸酯 (EGCG) 可以抑制动物模型中的肝脏炎症和纤维化，但其在 HCC 化学预防中的作用尚未得到充分证实。本研究中，雄性 Wistar 大鼠以 50 mg/kg 的剂量注射二乙基亚硝胺，持续 18 周以诱发肝硬化和 HCC，并在饮用水中以 0.02% 的浓度给予 EGCG。EGCG 临床可达到的剂量在二乙基亚硝胺损伤的大鼠中具有良好的耐受性，并且与改善的血清肝脏标志物有关，包括丙氨酸转氨酶、天冬氨酸转氨酶、和总胆红素，并减少 HCC 肿瘤的形成。对二乙基亚硝胺损伤的肝组织进行的转录组学分析发现，与 Hoshida 高风险 HCC 基因特征相关的基因表达增加，EGCG 治疗可以防止这种情况发生。EGCG 治疗还抑制了纤维化进展，这与肝星状细胞的失活和衰老相关分泌表型的诱导有关。总之，以临床安全剂量给药的 EGCG 在大鼠二乙基亚硝胺肝损伤模型中表现出化学预防和抗纤维化作用。这可以通过 EGCG 治疗来预防。EGCG 治疗还抑制了纤维化进展，这与肝星状细胞的失活和衰老相关分泌表型的诱导有关。总之，以临床安全剂量给药的 EGCG 在大鼠二乙基亚硝胺肝损伤模型中表现出化学预防和抗纤维化作用。这可以通过 EGCG 治疗来预防。EGCG 治疗还抑制了纤维化进展，这与肝星状细胞的失活和衰老相关分泌表型的诱导有关。总之，以临床安全剂量给药的 EGCG 在大鼠二乙基亚硝胺肝损伤模型中表现出化学预防和抗纤维化作用。