Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina.
Instituto de Fisiología Experimental (IFISE), Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina; Área Morfología, Facultad de Ciencias Bioquímicas y Farmacéuticas, UNR, Suipacha 570 (S2002LRL), Rosario, Argentina; Centro de Altos Estudios en Ciencias Humanas y de la Salud (CAECIHS) Sede Regional Rosario, Universidad Abierta Interamericana, Av. Pellegrini 1618 (S2000BUG), Rosario, Argentina.
Biochem Pharmacol. 2023 Jun;212:115573. doi: 10.1016/j.bcp.2023.115573. Epub 2023 Apr 29.
Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer worldwide. Therapeutic strategies are still challenging due to the high relapse rate after surgery and multidrug resistance (MDR). It is essential to better understand the mechanisms for HCC progression and MDR for the development of new therapeutic strategies. Mammalian sirtuins (SIRTs), a family of seven members, are related to tumor progression, MDR and prognosis and were proposed as potential prognostic markers, as well as therapeutic targets for treating cancer. SIRT1 is the most studied member and is overexpressed in HCC, playing an oncogenic role and predicting poor prognosis. Several manuscripts describe the role of SIRTs2-7 in HCC; most of them report an oncogenic role for SIRT2 and -7 and a suppressive role for SIRT3 and -4. The scenario is more confusing for SIRT5 and -6, since information is contradictory and scarce. For SIRT1 many inhibitors are available and they seem to hold therapeutic promise in HCC. For the other members the development of specific modulators has just started. This review is aimed to describe the features of SIRTs1-7 in HCC, and the role they play in the onset and progression of the disease. Also, when possible, we will depict the information related to the SIRTs modulators that have been tested in HCC and their possible implication in MDR. With this, we hope to clarify the role of each member in HCC and to shed some light on the most successful strategies to overcome MDR.
肝细胞癌（HCC）是全球癌症死亡的第三大常见原因。由于手术后复发率高和多药耐药（MDR），治疗策略仍然具有挑战性。更好地了解 HCC 进展和 MDR 的机制对于开发新的治疗策略至关重要。哺乳动物沉默调节蛋白（SIRTs）是一个由七个成员组成的家族，与肿瘤进展、MDR 和预后有关，并被提议作为潜在的预后标志物，以及治疗癌症的治疗靶点。SIRT1 是研究最多的成员，在 HCC 中过表达，发挥致癌作用并预测预后不良。有几篇论文描述了 SIRTs2-7 在 HCC 中的作用；它们中的大多数报告 SIRT2 和 -7 具有致癌作用，SIRT3 和 -4 具有抑制作用。SIRT5 和 -6 的情况更加混乱，因为信息相互矛盾且稀缺。对于 SIRT1，有许多抑制剂可用，它们似乎在 HCC 中具有治疗前景。对于其他成员，特定调节剂的开发才刚刚开始。本综述旨在描述 SIRTs1-7 在 HCC 中的特征，以及它们在疾病发生和进展中所起的作用。还将尽可能描述已在 HCC 中测试的 SIRTs 调节剂的信息及其对 MDR 的可能影响。通过这种方式，我们希望阐明每个成员在 HCC 中的作用，并为克服 MDR 提供最成功的策略。
