Effect of ginsenoside Rh2 on the migratory ability of HepG2 liver carcinoma cells: Recruiting histone deacetylase and inhibiting activator protein 1 transcription factors

Shi,Qingqiang; Li,Jing; Feng,Ziqiang; Zhao,Lvcui; Luo,Lian; You,Zhimei; Li,Danyang; Xia,Jing; Zuo,Guowei; Chen,Dilong

doi:10.3892/mmr.2014.2392

Effect of ginsenoside Rh2 on the migratory ability of HepG2 liver carcinoma cells: Recruiting histone deacetylase and inhibiting activator protein 1 transcription factors

Authors:
- Qingqiang Shi
- Jing Li
- Ziqiang Feng
- Lvcui Zhao
- Lian Luo
- Zhimei You
- Danyang Li
- Jing Xia
- Guowei Zuo
- Dilong Chen
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Affiliations: Laboratory of Stem Cell and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing 40016, P.R. China, Laboratory of Clinical Diagnostics, Chongqing Medical University, Chongqing 40016, P.R. China
Published online on: July 18, 2014 https://doi.org/10.3892/mmr.2014.2392
Pages: 1779-1785
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

In previous experiments, ginsenoside Rh2 induced apoptosis and cell cycle arrest, which indicates a potential role for ginsenoside Rh2 in anticancer treatment. The effect of ginsenoside Rh2 on cancer is marked and ginsenoside Rh2 has been shown to inhibit pancreatic tumor migratory ability. In the present study, Transwell chambers were used in order to investigate whether ginsenoside Rh2 inhibits the migratory ability of HepG2 liver carcinoma cells. Furthermore, to analyze activator protein 1 (AP‑1) transcription factor expression following Rh2 treatment, ten plasmids encoding Renilla luciferase coupled to the transcription factors were transiently transfected into the HepG2 cells and luciferase was detected by the Luciferase Reporter Assay system reagent. The results indicated that ginsenoside Rh2 inhibited HepG2 cell migratory ability. The expression levels of AP‑1 transcription factors were increased in HepG2 cells following induction by phorbol 12‑myristate 13‑acetate, but ginsenoside Rh2 suppressed this induced AP‑1 expression. AP‑1 transcription factors recruit histone deacetylase (HDAC)4 and affect its transcription, thus, the expression levels of HDAC4 were also analyzed, and these were found to be increased in the Rh2 treatment group. Matrix metalloproteinase 3 (MMP3), a gene downstream of AP‑1, was then investigated, and the treatment group expressed reduced levels of MMP3 gene and protein. Therefore, the inhibitory effect of ginsenoside Rh2 on the migratory ability of HepG2 may be presumed to occur by the recruitment of HDAC and the resulting inhibition of AP‑1 transcription factors, in order to reduce the expression levels of MMP3 gene and protein.

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