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

Lin, Chen; Chen, Dongfeng LU ; Gong, Mouchun; Na, Manli LU ; Li, Linfang; Wu, Hongping; Jiang, Lihua; Qian, Yanzhen; Fang, Guoen and Xue, Xuchao (2009) In Cancer Letters 284(2). p.141-148
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
therapy, Gene, Gastric cancer, Oncolytic adenovirus, TRAIL gene, Ad5/35 vector
in
Cancer Letters
volume
284
issue
2
pages
141 - 148
publisher
Elsevier
external identifiers
  • wos:000270530700004
  • scopus:69549126167
ISSN
1872-7980
DOI
10.1016/j.canlet.2009.04.026
language
English
LU publication?
yes
id
6bcb81e3-f543-4f81-9308-d8b4c7acbe1e (old id 1507499)
date added to LUP
2009-11-20 13:32:59
date last changed
2017-07-09 03:58:42
@article{6bcb81e3-f543-4f81-9308-d8b4c7acbe1e,
  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.},
  author       = {Lin, Chen and Chen, Dongfeng and Gong, Mouchun and Na, Manli and Li, Linfang and Wu, Hongping and Jiang, Lihua and Qian, Yanzhen and Fang, Guoen and Xue, Xuchao},
  issn         = {1872-7980},
  keyword      = {therapy,Gene,Gastric cancer,Oncolytic adenovirus,TRAIL gene,Ad5/35 vector},
  language     = {eng},
  number       = {2},
  pages        = {141--148},
  publisher    = {Elsevier},
  series       = {Cancer Letters},
  title        = {Concomitant use of Ad5/35 chimeric oncolytic adenovirus with TRAIL gene and taxol produces synergistic cytotoxicity in gastric cancer cells},
  url          = {http://dx.doi.org/10.1016/j.canlet.2009.04.026},
  volume       = {284},
  year         = {2009},
}