• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.298-309
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• 2000

Background : The antitumor effects of herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir (GCV) strategies for cancer gene therapy have a the following advantages : 1) a direct cytotoxicity to HSV-tk modified cancer cells by GCV 2) a cell death by the local transfer of toxic metabolites from the HSV-tk modified cells to nearby unmodified tumor cells (bystander effect), and 3) in vivo bystander effect such as antitumor-immunity. Retroviral and adenoviral sequences can silence transgene expression in cells and mice. In this study, we investigated the above described advantages of HSV-tk/GCV strategy in Lewis lung cell and mouse lung cancer model using retroviral vector and adenoviral vector. Also, we observed whether the expression of a silenced gene can be reactivated by treating cells with butyrate. Methods : Retrovirus-HSV-tk and adenovirus-HSV-tk vectors were used for the transduction of Lewis lung carcinoma (LLC) cells. The change of HSV-tk expression by butyrate was measured by Western blol The antitumor activities containing bystander effect were observed in vivo (by MTT assay) and in vivo tumor models of various combinations of LLC and LLC-tk. Results : 1. Butyrate induced the enhancement of HSV-tk expression from adenovirally transduced cells but not from retrovirally transduced cells. 2. Both retrovirus-HSV-tk and adenovirus-HSV-tk vectors with GCV treatment were effective for killing of tumor cell in vitro and suppression of LLC tumorigenicity. Bystander effect was responsible for killing of mixture of LLC-tk and LLC in vitro and in vivo-tumorigenicity model. Conclusion : Butyrate could augment adenovirus-mediated HSV -tk gene expression. Cancer gene therapy with HSV-tk suicide gene by retroviral and adenoviral vector seems to be an effective approach for lung cancer therapy.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.1
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• pp.143-148
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• 2003

Antitumorigenic and antimutagenic activities of the doenjangs prepared from mushroom mycelia-cultured traditional mejus (designated to MTDJ) were investigated using the model of Sarcoma-180-induced mouse ascites cancer, and 2-amino-3-methylimidazo ［4,5-f］ quinoline (IQ) and aflatoxin B$_1$ (AFB$_1$) -mediated S. typhimurium mutagenicity, respectively. Antioxidative activity of MTDJ was also investigated using the mouse liver microsome system. Mushroom stains used for the preparation of the mushroom mycelia-cultured traditional mejus were Synryeong (Agaricus blazei), Yeonggi (Canoderma Iucidum), Sanghwang (Phellinus linteus), and Neutari (Pleurotus ostreatus). All MTDJS showed the enhanced antitumorigenicities (12% by Synryeong, 13% by Sanghwang, 16% by Yeonggi, and 19% by Neutari), antimutagenicity (6.1~20.8% for IQ and 3.1~10.2% for AFB$_1$), and antioxidative activity (6.6~46.5%), relative to the control doenjang. The $\beta$-D-glucan content (0.75~1.71 mg/g) of MTDJs was 3~8 times higher than that (0.22 mg/g) of the control doenjang. Genistein content (769~932 Ug/g) of MTDJS was also higher than that (728 Ug/g) of control doenjang The content of $\beta$-D-glucan and genistein was not exactly correlated to the antitumorigenicity and antimutagenicity of MTDJs. These results indicate that anti-tumorigenicity and antimutagenicity of MTDJS were elevated in comparison with the control doenjang, and the observed functions were, in part, derived from $\beta$-glucan and/or genistein in the MTDJS.