mda-7/IL-24 induces apoptosis in human HepG2 hepatoma cells by endoplasmic reticulum stress

Xiaofeng Zhang1, Xiaoyan Kang, Lehua Shi

  • 1Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, People's Republic of China.

Oncology Reports
|July 19, 2008
PubMed

Insights

Adenovirus-mediated mda-7/IL-24 (Ad.mda-7) induces apoptosis in liver cancer cells by activating endoplasmic reticulum (ER) stress. Blocking ER stress inhibits Ad.mda-7

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The tumor suppressor gene mda-7/IL-24 exhibits broad-spectrum anticancer activity.
  • The precise molecular mechanisms underlying mda-7/IL-24-induced apoptosis remain incompletely understood and may vary by tumor type.

Purpose of the Study:

  • To investigate the apoptotic effects of adenovirus-mediated mda-7/IL-24 (Ad.mda-7) on human HepG2 hepatoma cells.
  • To elucidate the role of endoplasmic reticulum (ER) stress in Ad.mda-7-induced apoptosis in liver cancer.

Main Methods:

  • Adenovirus-mediated delivery of mda-7/IL-24 (Ad.mda-7) to HepG2 cells in vitro.
  • Inhibition of ER stress pathways to assess its impact on apoptosis.
  • In vivo studies using subcutaneous HepG2 tumor xenografts in mice.
  • Analysis of apoptosis-related gene expression (caspase-12, Bax, caspase-3).

Main Results:

  • Ad.mda-7 treatment induced apoptosis in HepG2 cells.
  • Blocking ER stress significantly inhibited Ad.mda-7-induced apoptosis and down-regulated key apoptotic markers (caspase-12, Bax, caspase-3).
  • Ad.mda-7 treatment inhibited tumor growth and angiogenesis in vivo, with ER stress inhibition preventing apoptosis in liver cancer cells.

Conclusions:

  • Ad.mda-7 primarily induces apoptosis in HepG2 liver cancer cells through the activation of the endoplasmic reticulum stress pathway.
  • Targeting ER stress represents a potential therapeutic strategy in conjunction with Ad.mda-7 for liver cancer treatment.

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