Browse

Nuclear factor-kappaB dependency of doxorubicin sensitivity in gastric cancer cells is determined by manganese superoxide dismutase expression

Cited 25 time in Web of Science Cited 27 time in Scopus
Authors
Cho, Sung Jin; Park, Jong-Wan; Kang, Jae Seung; Kim, Woo Ho; Juhnn, Yong-Sung; Lee, Jae-Seon; Kim, Young-Hoon; Ko, Yong San; Nam, Seon Young; Lee, Byung Lan
Issue Date
2008-03-31
Publisher
Japanese Cancer Association = 日本癌学会
Wiley-Blackwell
Citation
Cancer Sci 2008; 99: 1117-24
Description
The definitive version is available at www3.interscience.wiley.com.
Abstract
The role of nuclear factor-kappaB (NF-kappaB) activation in cancer cell apoptosis appears to be tailored specifically for each cell type and the type of NF-kappaB inducer. The present study aimed to determine whether or not NF-kappaB activation is associated with chemosensitivity to doxorubicin (DOX) using the DOX-sensitive SNU-601 and DOX-resistant SNU-216 gastric cancer cell lines. The effect of NF-kappaB activation on DOX (1 microg/mL) sensitivity was analyzed after the suppression of NF-kappaB activation using transfection of the super-suppressive mutant form of IkappaBalpha (mIkappaBalpha) or pretreatment with pyrrolidine dithiocarbamate. In addition, the association between NF-kappaB and manganese superoxide dismutase (MnSOD) in relation to DOX sensitivity was analyzed after the modulation of MnSOD expression. The NF-kappaB activity was much higher in DOX-resistant SNU-216 cells than in DOX-sensitive SNU-601 cells before and after DOX treatment. Overexpression of mIkappaBalpha or pyrrolidine dithiocarbamate pretreatment decreased the DOX resistance in SNU-601 cells with low MnSOD expression, but not in SNU-216 cells with high MnSOD expression. In comparison, the overexpression of MnSOD, which also suppressed NF-kappaB activation in both cell lines, increased DOX resistance in SNU-601 cells. Blocking of MnSOD expression using RNA interference techniques increased DOX sensitivity in SNU-216 cells, which was further augmented by the additional inhibition of NF-kappaB activity. Our results showed that whether NF-kappaB contributes to DOX sensitivity in gastric cancer cells is determined by the level of MnSOD expression. Thus, targeting both MnSOD and NF-kappaB may be helpful for increasing the efficacy of DOX treatment of DOX-resistant SNU gastric cancer cells.
ISSN
1347-9032 (print)
1349-7006 (online)
Language
English
URI
https://hdl.handle.net/10371/4443
DOI
https://doi.org/10.1111/j.1349-7006.2008.00789.x

https://doi.org/10.1111/j.1349-7006.2008.00789.x
Files in This Item:
There are no files associated with this item.
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Pathology (병리학전공)Journal Papers (저널논문_병리학전공)
  • mendeley

Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse