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Updated: Sep 17, 2025

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Acteoside suppresses hepatocellular carcinoma progression via modulation of macrophage migration inhibitory factor
Liu-Lu Gao1, Dong Jia2, Jia-Qi Shi2
1Department of Gastroenterology, Qin Huang Hospital, Xi'an 710600, Shaanxi, China.
Abstract:
This study investigated acteoside's (ACT) inhibition of hepatocellular carcinoma (HCC) progression via macrophage migration inhibitory factor (MIF) and MAPK signaling; immunohistochemistry and in situ hybridization assessed MIF/MAPK expression in HCC, cirrhotic, and normal tissues. The effects of ACT on HepG2 and Huh-7 cells were evaluated via CCK-8 assays, wound healing assays, and Transwell assays. Cell lines with MIF knockdown or overexpression were established to explore MIF's role. Western blotting analyzed autophagy, apoptosis, and metastasis-related proteins. A rat HCC model validated in vitro findings using PCR, immunohistochemistry, and Western blot analysis. The research results suggest that the expression of MIF and MAPK-related proteins is upregulated in HCC and cirrhotic tissues. ACT significantly suppressed HepG2 and Huh-7 cell proliferation, migration, and invasion. It downregulated MIF, p-ERK, N-cadherin, VEGF, and Bcl-2 while upregulating p-JNK, p-p38 MAPK, Beclin-1, LC3B, Bax, and E-cadherin. In vivo, ACT reduced MIF, p-ERK, Bcl-2, and MMP-2 expression and increased p-JNK and p-p38 MAPK levels. Based on the above results, this study concludes that the progression of HCC progression is associated with elevated MIF and MAPK activation. ACT suppresses HCC by modulating MIF and altering MAPK phosphorylation, promoting autophagy and apoptosis while inhibiting invasion and migration.
Insights
Acteoside (ACT) inhibits hepatocellular carcinoma (HCC) by targeting macrophage migration inhibitory factor (MIF) and MAPK signaling pathways. This natural compound suppresses tumor growth, migration, and invasion, offering a potential therapeutic strategy for HCC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) progression is linked to elevated macrophage migration inhibitory factor (MIF) and mitogen-activated protein kinase (MAPK) signaling.
- Understanding the molecular mechanisms underlying HCC is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the inhibitory effects of acteoside (ACT) on hepatocellular carcinoma (HCC) progression.
- To elucidate the roles of MIF and MAPK signaling pathways in ACT's anti-cancer activity.
Main Methods:
- Immunohistochemistry, in situ hybridization, CCK-8, wound healing, Transwell assays, Western blotting, PCR, and a rat HCC model were employed.
- MIF knockdown and overexpression cell lines were utilized to assess MIF's function.
- Analysis included cell proliferation, migration, invasion, autophagy, apoptosis, and metastasis-related protein expression.
Main Results:
- MIF and MAPK signaling proteins were upregulated in HCC and cirrhotic tissues.
- ACT significantly inhibited HCC cell proliferation, migration, and invasion in vitro.
- ACT modulated key proteins involved in autophagy, apoptosis, and metastasis, both in vitro and in vivo.
Conclusions:
- HCC progression is associated with increased MIF and MAPK activation.
- Acteoside suppresses HCC by downregulating MIF and modulating MAPK phosphorylation.
- ACT promotes autophagy and apoptosis while inhibiting invasion and migration, presenting a potential therapeutic avenue for HCC.
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