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ID 49554
フルテキストURL
著者
Hashimoto, Yuuri Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Tazawa, Hiroshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Teraishi, Fuminori Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Kojima, Toru Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Watanabe, Yuichi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Uno, Futoshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Yano, Shuya Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Urata, Yasuo Oncolys BioPharma Inc
Kagawa, Shunsuke Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol
Fujiwara, Toshiyoshi Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Surg Gastroenterol ORCID 科研費研究者番号
抄録
Hypoxia is a microenvironmental factor that contributes to the invasion, progression and metastasis of tumor cells. Hypoxic tumor cells often show more resistance to conventional chemoradiotherapy than normoxic tumor cells, suggesting the requirement of novel antitumor therapies to efficiently eliminate the hypoxic tumor cells. We previously generated a tumor-specific replication-competent oncolytic adenovirus (OBP-301: Telomelysin), in which the human telomerase reverse transcriptase (hTERT) promoter drives viral E1 expression. Since the promoter activity of the hTERT gene has been shown to be upregulated by hypoxia, we hypothesized that, under hypoxic conditions, the antitumor effect of OBP-301 with the hTERT promoter would be more efficient than that of the wild-type adenovirus 5 (Ad5). In this study, we investigated the antitumor effects of OBP-301 and Ad5 against human cancer cells under a normoxic (20% oxygen) or a hypoxic (1% oxygen) condition. Hypoxic condition induced nuclear accumulation of the hypoxia-inducible factor-1 alpha and upregulation of hTERT promoter activity in human cancer cells. The cytopathic activity of OBP-301 was significantly higher than that of Ad5 under hypoxic condition. Consistent with their cytopathic activity, the replication of OBP-301 was significantly higher than that of Ad5 under the hypoxic condition. OBP-301-mediated E1A was expressed within hypoxic areas of human xenograft tumors in mice. These results suggest that the cytopathic activity of OBP-301 against hypoxic tumor cells is mediated through hypoxia-mediated activation of the hTERT promoter. Regulation of oncolytic adenoviruses by the hTERT promoter is a promising antitumor strategy, not only for induction of tumor-specific oncolysis, but also for efficient elimination of hypoxic tumor cells.
発行日
2012-06-15
出版物タイトル
PLoS ONE
7巻
6号
ISSN
1932-6203
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1371/journal.pone.0039292
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/49126
言語
English
論文のバージョン
publisher
査読
有り
DOI
Web of Sience KeyUT