Concomitant use of Ad5/35 chimeric oncolytic adenovirus with TRAIL gene and taxol produces synergistic cytotoxicity in gastric cancer cells

Chen Lin, Dongfeng Chen, Mouchun Gong, Manli Na, Linfang Li, Hongping Wu, Lihua Jiang, Yanzhen Qian, Guoen Fang, Xuchao Xue

Research output: Contribution to journalArticlepeer-review

20 Citations (SciVal)

Abstract

Chimeric adenoviral vectors possessing fiber derived from human adenovirus subgroup B (Ad35) have been developed for their high infection efficiency in cell types which are refractory to adenovirus serotype 5 (Subgroup C) The present study constructed an E1B-deleted chimeric oncolytic adenovirus, SG235-TRAIL, which carries a human TRAIL gene expression cassette and whose fiber shaft and knob domains are from serotype AM. It was found that SG235-TRAIL preferentially replicated in gastric cancer cell lines, SGC-7901 and BGC-823 compared to in normal human fibroblast BJ cells. Also, when compared with a replication-deficient chimeric vector Ad5/35-TRAIL, SG235-TRAIL mediated a higher level of the transgene expression via viral replication in the cancer cells. Further, because of the more efficient cell-entry and infection, SG235-TRAIL induced stronger cell apoptosis than the Ad5 CRAD vector, ZD55-TRAIL In addition, SG235-TRAIL in combination with the chemotherapeutic drug, taxol, produced a synergistic cytotoxic effect in cancer cells in vitro without causing significant toxicity to normal cells. In the gastric tumor xenograft mouse model, intratumoral SG235-TRAIL injection produced a significant antitumor effect 14 days after treatment. Pathological examination demonstrated TRAIL expression and associated apoptosis in majority of SG235-TRAIL-treated tumor cells. These results suggest that SG235-TRAIL is a potential novel, efficient anti-cancer agent, and in combination with taxol, it would be even more useful with considerably low toxic side effects. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)141-148
JournalCancer Letters
Volume284
Issue number2
DOIs
Publication statusPublished - 2009

Subject classification (UKÄ)

  • Cancer and Oncology

Keywords

  • therapy
  • Gene
  • Gastric cancer
  • Oncolytic adenovirus
  • TRAIL gene
  • Ad5/35 vector

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