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Published on: March 22, 2011
Adenoviral gene transduction of hepatocyte growth factor elicits inhibitory effects for hepatoma
Kentaro Yuge1, Tomoyuki Takahashi, Satoshi Nagano
1Department of Gene Therapy and Regenerative Medicine, Gifu University School of Medicine, Japan.
Abstract:
Hepatocyte growth factor (HGF) gene therapy may have potential for treating chronic hepatitis (CH) and liver cirrhosis (LC). However, the lack of an HGF gene therapy study on hepatomas that are often associated with CH or LC, together with the stimulatory effects of HGF on many types of cancer, may hamper its application. This study explored the effects of adenoviral HGF gene transduction and their mechanisms on two types of hepatoma cells (hepatoblastoma and hepatocellular carcinoma) in in vitro experiments. Both types of hepatomas were revealed to have higher adenoviral gene transduction efficiencies and more efficient expressions of the HGF transgene, which successfully activated the HGF receptor/c-Met in an autocrine fashion, than those of other types of cancer. Notably, not only HGF, but also adenoviral infection, inhibited DNA synthesis, whereas only HGF but not adenoviral infection exerted a potent apoptotic effect. Moreover, adenoviral HGF gene transduction additively exerted inhibitory effects on cisplatin-treated hepatomas. In conclusion, inhibitory and apoptotic effects of adenoviral HGF gene transduction in hepatomas in contrast to potent mitogenic and antiapoptotic effects of HGF for hepatocytes are not only of biological interest, but also pose clinical benefits for adenoviral HGF gene therapy for CH and LC.
Insights
Adenoviral Hepatocyte Growth Factor (HGF) gene therapy shows promise for treating liver diseases. In vitro studies reveal HGF gene transduction inhibits hepatoma cell growth and induces apoptosis, suggesting therapeutic potential.
Area of Science:
- Hepatology
- Gene Therapy
- Oncology
Background:
- Hepatocyte Growth Factor (HGF) gene therapy is explored for chronic hepatitis (CH) and liver cirrhosis (LC).
- HGF's known stimulatory effects on cancer growth and limited studies on hepatomas pose application challenges.
Purpose of the Study:
- To investigate the effects and mechanisms of adenoviral HGF gene transduction on hepatoblastoma and hepatocellular carcinoma cells in vitro.
- To evaluate the potential of HGF gene therapy for hepatomas associated with CH or LC.
Main Methods:
- In vitro experiments using two hepatoma cell lines.
- Adenoviral HGF gene transduction.
- Analysis of HGF receptor/c-Met activation.
- Assessment of DNA synthesis and apoptosis.
- Evaluation of combined effects with cisplatin treatment.
Main Results:
- Hepatoma cells exhibited high adenoviral gene transduction and HGF transgene expression efficiencies.
- HGF activated the HGF receptor/c-Met in an autocrine manner.
- Both HGF and adenoviral infection inhibited DNA synthesis; HGF induced apoptosis.
- Adenoviral HGF gene transduction showed additive inhibitory effects on cisplatin-treated hepatomas.
Conclusions:
- Adenoviral HGF gene transduction demonstrates inhibitory and apoptotic effects on hepatomas in vitro.
- These findings contrast with HGF's known mitogenic effects on hepatocytes.
- Results suggest potential clinical benefits for adenoviral HGF gene therapy in treating CH, LC, and associated hepatomas.
