Department of Hepatopancreatobiliary Surgery, Hangzhou First People's Hospital, The Affiliated Hospital of Medical School of Zhejiang University, Hangzhou, 310006, Zhejiang, China.
Naunyn Schmiedebergs Arch Pharmacol. 2019 Dec;392(12):1551-1560. doi: 10.1007/s00210-019-01701-7. Epub 2019 Jul 29.
Hepatocellular carcinoma (HCC) patients have low 5-year survival due to the delayed diagnosis, so it is necessary to develop an alternative treatment. Preferentially expressed antigen of melanoma (PRAME) has a high expression in HCC patients, and the effects of evodiamine on HCC are less characterized, although evodiamine has anti-tumor activities in several tumor types. To investigate the effects of evodiamine on PRAME expression, the in vitro PRAME expression in HepG2 cells after incubated with evodiamine was determined by RT-PCR and western blot. Cell viability, migration, invasion, and apoptosis of evodiamine-incubated HepG2 cells were evaluated by Cell Counting Kit-8, wound healing, transwell assay, and Annexin V-FITC/PI double-staining assay, respectively. To evaluate the mechanism of the regulation of evodiamine on the PRAME expression, chromatin immunoprecipitation coupled with quantitative PCR was employed. Xenograft model was used to evaluate the effects of evodiamine on tumor growth, survival rate, and the PRAME expression. The PRAME expression was inhibited in evodiamine-treated HepG2 cells in vitro and in vivo. The tumor metastasis and growth were inhibited resulting from evodiamine incubation. The evodiamine inhibited the PRAME expression through trimethylation of H3K27. In this study, evodiamine contributes to in vitro and in vivo tumor cell growth inhibition. To achieve this inhibition, the PRAME expression may be repressed through trimethylation resulting from epigenetic regulation of evodiamine.
肝细胞癌（HCC）患者的 5 年生存率较低，这是由于诊断延迟，因此有必要开发替代治疗方法。黑色素瘤优先表达抗原（PRAME）在 HCC 患者中高表达，而尽管依诺霉素在几种肿瘤类型中具有抗肿瘤活性，但依诺霉素对 HCC 的作用特征较少。为了研究依诺霉素对 PRAME 表达的影响，通过 RT-PCR 和 Western blot 测定了用依诺霉素孵育后 HepG2 细胞中体外的 PRAME 表达。通过细胞计数试剂盒-8、划痕愈合、Transwell 测定和 Annexin V-FITC/PI 双重染色测定分别评估了依诺霉素孵育的 HepG2 细胞的细胞活力、迁移、侵袭和凋亡。为了评估依诺霉素对 PRAME 表达的调节机制，采用染色质免疫沉淀结合定量 PCR 进行了评估。采用异种移植模型评估了依诺霉素对肿瘤生长、存活率和 PRAME 表达的影响。依诺霉素在体外和体内抑制了 HepG2 细胞中的 PRAME 表达。依诺霉素孵育抑制了肿瘤转移和生长。依诺霉素通过 H3K27 的三甲基化抑制了 PRAME 的表达。在这项研究中，依诺霉素有助于体外和体内肿瘤细胞的生长抑制。为了实现这种抑制，PRAME 表达可能通过依诺霉素的表观遗传调节导致的三甲基化而受到抑制。
