Oncolytic adenovirus-mediated MDA-7/IL-24 overexpression enhances antitumor activity in hepatocellular carcinoma cell

Chao-Wen Xiao1, Xin-Bo Xue, Hui Zhang

  • 1Department of General Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.

Abstract

Insights

The oncolytic adenovirus SG600-IL24 effectively suppresses hepatocellular carcinoma cell growth and induces apoptosis. This novel therapy shows selective antitumor activity, sparing normal liver cells.

Area of Science:

  • Oncology
  • Gene Therapy
  • Molecular Biology

Background:

  • Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24) is a tumor suppressor gene with broad-spectrum anticancer activity.
  • Hepatocellular carcinoma (HCC) remains a significant global health challenge, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To evaluate the efficacy of replication-competent oncolytic adenovirus SG600-IL24 and replication-incompetent adenovirus Ad.IL-24, both expressing MDA-7/IL-24, against HCC cell lines.
  • To compare the antitumor effects of SG600-IL24 and Ad.IL-24 in vitro.

Main Methods:

  • HCC cell lines (HepG2, Hep3B, SMMC-7721, HCCLM3) and normal liver cells (L02) were infected with SG600-IL24 and Ad.IL-24.
  • Gene expression was confirmed via RT-PCR, ELISA, and Western blotting. Cell proliferation and apoptosis were assessed using MTT assays, Hoechst, and Annexin-V/PI staining. Cell cycle analysis was performed by flow cytometry.

Main Results:

  • SG600-IL24 demonstrated high expression of exogenous MDA-7/IL-24 in infected cells.
  • SG600-IL24 significantly inhibited proliferation, induced apoptosis, and caused G2/M phase arrest in HCC cell lines.
  • These effects were not observed in the normal liver cell line L02.

Conclusions:

  • SG600-IL24 exhibits selective in vitro antitumor activity against HCC cell lines by inducing growth suppression and apoptosis.
  • SG600-IL24 significantly enhances antitumor efficacy in HCC compared to Ad.IL-24.

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