Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey, Department of Surgery, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
Carnegie Vanguard High School, Houston, TX 77019, USA.
Oncol Rep. 2019 Jan;41(1):143-153. doi: 10.3892/or.2018.6793. Epub 2018 Oct 15.
Hepatoblastoma is the most common malignant liver tumor in children. Since it is often unresectable and exhibits drug resistance, the treatment of advanced hepatoblastoma is challenging. The orphan nuclear receptor liver receptor homolog‑1 (LRH‑1) serves prominent roles in malignancy; however, to the best of our knowledge, the role of LRH‑1 in hepatoblastoma remains unknown. In the present study, human hepatoblastoma cell lines were analyzed; the mRNA and protein expression levels of LRH‑1 were significantly higher in HepG2 and HuH6 cells compared with those in HepT1 cells and control THLE‑2 cells. Knockdown of LRH‑1 resulted in decreased HepG2 and HuH6 cell proliferation via downregulation of cyclin D1 (CCND1) and c‑Myc. Furthermore, treatment with an LRH‑1 antagonist (LRA) inhibited the proliferation and colony formation of cell lines in a dose‑dependent manner, and induced cell cycle arrest at G1 phase through inhibition of CCND1 expression. Finally, LRA treatment enhanced the cytotoxic effects of doxorubicin on hepatoblastoma cells. Collectively, these findings suggested that LRH‑1 may have an important role in the progression of hepatoblastoma and implicated LRA as a novel, potential therapeutic agent for the treatment of hepatoblastoma.
肝癌是儿童中最常见的恶性肝肿瘤。由于其通常不可切除并表现出耐药性，因此晚期肝癌的治疗具有挑战性。孤儿核受体肝受体同系物 1 (LRH-1) 在恶性肿瘤中发挥着重要作用；然而，据我们所知，LRH-1 在肝癌中的作用尚不清楚。在本研究中，分析了人肝癌细胞系；与 HepT1 细胞和对照 THLE-2 细胞相比，LRH-1 在 HepG2 和 HuH6 细胞中的 mRNA 和蛋白表达水平显著更高。LRH-1 的敲低通过下调细胞周期蛋白 D1 (CCND1) 和 c-Myc 导致 HepG2 和 HuH6 细胞增殖减少。此外，LRH-1 拮抗剂 (LRA) 的处理以剂量依赖性方式抑制细胞系的增殖和集落形成，并通过抑制 CCND1 表达诱导细胞周期停滞在 G1 期。最后，LRA 处理增强了多柔比星对肝癌细胞的细胞毒性作用。总之，这些发现表明 LRH-1 可能在肝癌的进展中具有重要作用，并暗示 LRA 是治疗肝癌的一种新型潜在治疗剂。
