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.
Abstract:
mda-7/IL-24 shows tumor-suppressor activity in a broad spectrum of human cancer cells. However, the molecular mechanism by which mda-7/IL-24 induces apoptosis is not well understood and most likely involves different pathways depending on the tumor. We examined the apoptotic effect of the adenovirus-mediated mda-7/IL-24 (Ad.mda-7) on human HepG2 hepatoma cells. We found that blocking the endoplasmic reticulum (ER) stress inhibited apoptosis induced by Ad.mda-7 and down-regulated the expression of caspase-12, Bax and caspase-3. The treatment of subcutaneous tumor xenografts of HepG2 cells with Ad.mda-7 inhibited tumor growth and angiogenesis. As in the in vitro studies, we found that blocking ER stress prevented Ad.mda-7 from inducing apoptosis in liver cancer cells in vivo. Our studies suggest that Ad.mda-7 induces apoptosis of HepG2 cells mainly through activation of the ER stress pathway.
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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