Combination with low-dose gemcitabine and hTERT-promoter-dependent conditionally replicative adenovirus enhances cytotoxicity through their crosstalk mechanisms in pancreatic cancer

Manabu Onimaru, Kenoki Ohuchida, Eishi Nagai, Kazuhiro Mizumoto, Takuya Egami, Lin Cui, Norihiro Sato, Junji Uchino, Koichi Takayama, Makoto Hashizume, Masao Tanaka

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To overcome the limited clinical efficacy of conditionally replicative adenoviruses (CRAds), we investigated the effects of combination therapy with gemcitabine (GEM) and the hTERT-promoter-dependent CRAd (hTERT-CRAd), Ad5/3hTERTE1. This combination therapy exhibited enhanced cytotoxic effects on pancreatic cancer both in vitro and in vivo. Furthermore, we revealed that this enhancement effect was due to the multiple bidirectional interactions between hTERT-CRAd and GEM. The GEM-sensitizing effect of E1 expression derived from hTERT-CRAd, and the enhancement effect by GEM on hTERT promoter activity which led to the increase of adenovirus E1 and viral infectivity. This combination therapy may be a promising therapeutic approach for pancreatic cancer.

Original languageEnglish
Pages (from-to)178-186
Number of pages9
JournalCancer Letters
Issue number2
Publication statusPublished - Aug 1 2010


All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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