Homoharringtonine (HHT), was first isolated from the bark of Cephalotaxus harringtonia (Knight ex J. Forbes) K. Koch and Cephalotaxus fortunei Hook trees. The bark extract is used to treat leukemia and in recent years has also been used in traditional Chinese medicine (TCM) to treat solid tumors. However, the inhibitory mechanism of HHT in the progression of hepatocellular carcinoma (HCC) is rarely studied. We aimed to evaluate the antitumor efficacy of HHT on HCC in vitro and in vivo and elucidate the underlying molecular mechanism(s). HCC cell lines, including HCCLM3, HepG2 and Huh7, were used to evaluate the antitumor efficacy of HHT in vitro. Cytotoxicity and proliferative ability were evaluated by MTT and colony formation assays. Cell cycle progression and apoptosis in HHT-treated HCC cells were evaluated by flow cytometry. To determine the migration and invasion abilities of HCC cells, wound-healing and Transwell assays were used. Finally, Western blot analysis was used to reveal the proteins involved. We also established a xenograft nude mouse model for in vivo assessments of the preclinical efficacy of HHT, mainly using hematoxylin and eosin staining, immunohistochemistry, ultrasound imaging (USI) and magnetic resonance imaging (MRI). HHT suppressed the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells and induced cell cycle arrest at G2 phase and apoptosis. In the HCC xenograft model, HHT showed an obvious tumor suppressive effect. Surprisingly, Slug expression was also decreased by HHT via the PI3K/AKT/GSK3β signaling pathway at least partially suppressed the growth of HCC via the PI3K/AKT/GSK3β/Slug signaling pathway.

中文翻译：

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Homoharringtonine 通过抑制 PI3K/AKT/GSK3β/Slug 信号通路抑制肝细胞癌的进展。

Homoharringtonine (HHT)，首先从 Cephalotaxus harringtonia (Knight ex J. Forbes) K. Koch 和 Cephalotaxus Fortunei Hook 树的树皮中分离出来。树皮提取物用于治疗白血病，近年来也被用于中药（TCM）治疗实体瘤。然而，很少研究HHT在肝细胞癌（HCC）进展中的抑制机制。我们旨在评估 HHT 在体外和体内对 HCC 的抗肿瘤功效，并阐明潜在的分子机制。HCC 细胞系，包括 HCCLM3、HepG2 和 Huh7，用于评估 HHT 的体外抗肿瘤功效。通过 MTT 和集落形成试验评估细胞毒性和增殖能力。通过流式细胞术评估 HHT 处理的 HCC 细胞中的细胞周期进程和细胞凋亡。为了确定 HCC 细胞的迁移和侵袭能力，使用了伤口愈合和 Transwell 试验。最后，使用蛋白质印迹分析揭示所涉及的蛋白质。我们还建立了用于体内评估 HHT 临床前疗效的异种移植裸鼠模型，主要使用苏木精和伊红染色、免疫组织化学、超声成像 (USI) 和磁共振成像 (MRI)。HHT 抑制 HCC 细胞的增殖、迁移、侵袭和上皮间质转化 (EMT)，并诱导细胞周期停滞在 G2 期和细胞凋亡。在 HCC 异种移植模型中，HHT 显示出明显的肿瘤抑制作用。令人惊讶的是，HHT 也通过 PI3K/AKT/GSK3β 信号通路降低了 Slug 表达，至少部分抑制了 HCC 通过 PI3K/AKT/GSK3β/Slug 信号通路的生长。