Open Access

Effects of recombinant human adenovirus-p53 on the regression of hepatic fibrosis

  • Authors:
    • Yehong Liu
    • Puye Yang
    • Na Chen
    • Shumei Lin
    • Min Liu
  • View Affiliations

  • Published online on: August 26, 2016     https://doi.org/10.3892/ijmm.2016.2716
  • Pages: 1093-1100
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Hepatic fibrosis is a scarring process that may progress to hepatic cirrhosis and even hepatic carcinoma if left untreated. Hepatic stellate cells (HSCs) play essential roles in the development of hepatic fibrosis. The tumor suppressor protein p53 is a transcription factor that is involved in cell proliferation, cell cycle regulation, apoptosis and DNA repair. Recombinant human adenovirus-p53 (Ad-p53) has been demonstrated to act as a promising antitumor gene therapy in various types of cancer. However, there is limited infomration regarding the therapeutic effect of Ad-p53 on the regression of hepatic fibrosis. In order to examine the underlying molecular mechanism responsible for the effects of Ad-p53 on HSCs, a rat model of hepatic fibrosis was established and HSC-T6 cells were cultured under different conditions. The expression of p53, transforming growth factor (TGF-β1) and α-smooth muscle actin (α-SMA), which is a marker of activated HSCs, was detected by immunohistochemical assays and RT-qPCR. In vitro, five different concentrations (1x106, 5x106, 1x107, 2x107 and 5x107 PFU/ml) of Ad-p53 were selected for use in the MTT assay to analyze the proliferation of HSCs at 0, 24, 48 and 72 h. Flow cytometric analysis was applied to determine the effect of three different concentrations of Ad-p53 (5x106, 1x107 and 2x107 PFU/ml) on the cell cycle and the apoptosis of HSC-T6 cells at 24 and 48 h. The results of immunohistochemical studies and RT-qPCR showed that Ad-p53 upregulated the expression of p53, and downregulated the expression of TGF-β1 and α-SMA. The MTT assay revealed that when treated with various doses of Ad-p53, the proliferation of HSCs was inhibited within a certain range of concentrations and time periods. Analysis of flow cytometric data showed that Ad-p53 arrested the cell cycle in G1 phase and significantly induced apoptosis. Taken together, these findings suggest that Ad-p53 promotes apoptosis and inhibits the proliferation of HSCs in a time‑ and dose-dependent manner by modulating the expression of p53, TGF-β1 and α-SMA.

Related Articles

Journal Cover

October-2016
Volume 38 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Yang P, Chen N, Lin S and Liu M: Effects of recombinant human adenovirus-p53 on the regression of hepatic fibrosis. Int J Mol Med 38: 1093-1100, 2016.
APA
Liu, Y., Yang, P., Chen, N., Lin, S., & Liu, M. (2016). Effects of recombinant human adenovirus-p53 on the regression of hepatic fibrosis. International Journal of Molecular Medicine, 38, 1093-1100. https://doi.org/10.3892/ijmm.2016.2716
MLA
Liu, Y., Yang, P., Chen, N., Lin, S., Liu, M."Effects of recombinant human adenovirus-p53 on the regression of hepatic fibrosis". International Journal of Molecular Medicine 38.4 (2016): 1093-1100.
Chicago
Liu, Y., Yang, P., Chen, N., Lin, S., Liu, M."Effects of recombinant human adenovirus-p53 on the regression of hepatic fibrosis". International Journal of Molecular Medicine 38, no. 4 (2016): 1093-1100. https://doi.org/10.3892/ijmm.2016.2716