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Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

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neo_2021_210113N57

Title: Homoharringtonine inhibits the progression of hepatocellular carcinoma by suppressing the PI3K/AKT/GSK3β/Slug signaling pathway
Author: Hong-Yuan Liu, Tian-Xiu Dong, Zi-Zhuo Li, Tian-Tian Li, Jian Jiang, Ming-Wei Zhu, Ting-Ting An, Yao-Dong Chen, Xiu-Hua Yang

Abstract: 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.

Keywords: homoharringtonine; hepatocellular carcinoma; EMT; PI3K/AKT/GSK3β/Slug signaling pathway
Published online: 17-May-2021
Year: , Volume: , Issue: Page From: , Page To:
doi:10.4149/neo_2021_210113N57


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