Adenoviral gene transduction of hepatocyte growth factor elicits inhibitory effects for hepatoma
| Autor: | Satoshi Nagano, Yasuhiro Terazaki, Ngin Cin Khai, Hisayoshi Fujiwara, Takao Kawai, Ken-ichiro Kosai, Kentaro Yuge, Hiroaki Ushikoshi, Tomoyuki Takahashi, Toshikazu Nakamura, Yoshiteru Murofushi |
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| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Carcinoma Hepatocellular Time Factors Cell Survival Genetic enhancement Transgene Tetrazolium Salts Enzyme-Linked Immunosorbent Assay Biology Viral vector Adenoviridae Transduction (genetics) Cell Line Tumor medicine In Situ Nick-End Labeling Humans Phosphorylation Autocrine signalling Cell Proliferation Oncogene DNA synthesis Dose-Response Relationship Drug Caspase 3 Hepatocyte Growth Factor DNA Genetic Therapy Proto-Oncogene Proteins c-met Enzyme Activation Oncology Bromodeoxyuridine Caspases Cancer research Hepatocyte growth factor Cisplatin medicine.drug HeLa Cells |
| Zdroj: | International journal of oncology. 27(1) |
| ISSN: | 1019-6439 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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