Caveolin-1プロモーターを用いたHerpes Simplex Virus-thymidine kinase遺伝子発現アデノウィルスによる前立腺癌遺伝子治療における有効性と安全性の検討

The efficacy and toxicity of adenoviral vectors that express Herpes Simplex Virus-thymidine kinase (HSV-tk) gene under the transcriptional control of caveolin-1 promoter (cav.-1-tk) was compared to Cytomegalovirus (CMV) promoter or Rous sarcoma virus (RSV) promoter HSV-tk for prostate cancer. The cav.-1-tk demonstrated the strong cytotoxicity in vitro for mouse human prostate cancer cell line (178BMA) and human prostate cancer cell line (PC-3), which overxpress caveolin-1 levels. On the other hand, the cytotoxicity was weak for mouse (178PA) and human (LNCaP) prostate cancer cell line, which express low caveolin-1 levels. The antitumor efficacy was observed in each vector in vivo orthotopic model using 178BMA prostate cancer cell line. The immunohistochemical analysis results indicated that not only cancer cells but also tumor vasculature were destroyed by cav.-1-tk. The serum AST levels of cav.-1-tk was minimal change following intravenous injection. Taken together, adenovirus-mediated HSV-tk in situ gene therapy under the transcriptional control of caveolin-1 promoter may be effective and safe for prostate cancer compared to CMV or RSV promoter HSV-tk adenoviral vectors.

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