Open Access

Secretory expression of Par-4 SAC-HA2TAT following adeno-associated virus-mediated gene transfer induces apoptosis in HepG2 cells

  • Authors:
    • Tian-Jie Qin
    • Wei Ma
    • Shan-Xi Liu
    • Guang-Xiao Yang
    • Quan-Ying Wang
    • Xin-Han Zhao
  • View Affiliations

  • Published online on: July 26, 2010     https://doi.org/10.3892/mmr.2010.343
  • Pages: 749-757
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Abstract

Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal cells. The cancer-specific pro-apoptotic action of Par-4 is encoded in its centrally located SAC domain. In this study, to further enhance the anti-cancer effect of Par-4 in order to overcome the limitations of peptide therapy, a recombinant adeno-associated virus was constructed using the following strategies: the secretory expression of therapeutic peptide, a HA2TAT-mediated cytosolic delivery technique, and an adeno-associated virus gene transfer system. To test the hypothesis that Par-4 has an additive bystander effect as an anti-cancer therapy, we designed a secretory protein by adding a secretory signal peptide NT4(Si) to the Par-4 SAC-HA2TAT peptide gene sequence [NT4(Si)-Par-4 SAC-HA2TAT]. The results indicated that, compared to the normal NIH3T3 cell line, AAV-NT4(Si)-Par-4 SAC-HA2TAT significantly suppressed cell growth and induced rapid cell death in HepG2 cells in a time-dependent manner through successful gene transfer and secretory expression of therapeutic peptide at 48 h post-transfection. In addition, the secretory properties of Par-4 may greatly increase its effectiveness in cancer therapy when delivered in vivo.

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September-October 2010
Volume 3 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Qin T, Ma W, Liu S, Yang G, Wang Q and Zhao X: Secretory expression of Par-4 SAC-HA2TAT following adeno-associated virus-mediated gene transfer induces apoptosis in HepG2 cells. Mol Med Rep 3: 749-757, 2010.
APA
Qin, T., Ma, W., Liu, S., Yang, G., Wang, Q., & Zhao, X. (2010). Secretory expression of Par-4 SAC-HA2TAT following adeno-associated virus-mediated gene transfer induces apoptosis in HepG2 cells. Molecular Medicine Reports, 3, 749-757. https://doi.org/10.3892/mmr.2010.343
MLA
Qin, T., Ma, W., Liu, S., Yang, G., Wang, Q., Zhao, X."Secretory expression of Par-4 SAC-HA2TAT following adeno-associated virus-mediated gene transfer induces apoptosis in HepG2 cells". Molecular Medicine Reports 3.5 (2010): 749-757.
Chicago
Qin, T., Ma, W., Liu, S., Yang, G., Wang, Q., Zhao, X."Secretory expression of Par-4 SAC-HA2TAT following adeno-associated virus-mediated gene transfer induces apoptosis in HepG2 cells". Molecular Medicine Reports 3, no. 5 (2010): 749-757. https://doi.org/10.3892/mmr.2010.343