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Combination of radiotherapy and adenovirus-mediated p53 gene therapy for MDM2-overexpressing hepatocellular carcinoma

Authors
 Woong Sub KOOM  ;  Soo-Yeon PARK  ;  Wonwoo KIM  ;  Minjung KIM  ;  Ji-Seong KIM  ;  Hyunki KIM  ;  Il-Kyu CHOI  ;  Chae-Ok YUN  ;  Jinsil SEONG 
Citation
 Journal of Radiation Research, Vol.53(2) : 202-210, 2012 
Journal Title
 Journal of Radiation Research 
ISSN
 0449-3060 
Issue Date
2012
Abstract
The p53 gene plays a determinant role in radiation-induced cell death and its protein product is negatively regulated by MDM2. We investigated whether adenovirus-mediated modified p53 gene transfer, which blocks p53-MDM2 binding, is effective for radiation-induced cell death in hepatocellular carcinoma (HCC) at different MDM2 cellular levels. Human hepatocellular carcinoma cell lines expressing MDM2 at low levels (Huh7) and high levels (SK-Hep1) were used. Ad-p53 and Ad-p53vp are replication-deficient adenoviral vectors containing human wild-type or modified p53, respectively. The anti-tumor effect was highest for Ad-p53 + radiotherapy (RT) in the low-level MDM2 cells, whereas this effect was highest for Ad-p53vp + RT in the MDM2-overexpressing cells. In Huh-7 cells, Ad-p53 + RT decreased cell viability (32%) in vitro and inhibited tumor growth (enhancement factor, 1.86) in vivo. Additionally, p21 expression and apoptosis were increased. In contrast, in SK-Hep1 cells, Ad-p53vp + RT showed decreased cell viability (51%) in vitro and inhibition of tumor growth (enhancement factor, 3.07) in vivo. Caspase-3 expression and apoptosis were also increased. Adenovirus-expressing modified p53, which blocks p53-MDM2 binding, was effective in killing tumor cells overexpressing MDM2. Furthermore, the combination strategy for disruption of the p53-MDM2 interaction with RT demonstrated enhanced anti-tumor effects both in vitro and in vivo.
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DOI
10.1269/jrr.11110
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터)
1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Institute for Cancer Research (암연구소)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
Yonsei Authors
금웅섭(Koom, Woong Sub) ORCID logo https://orcid.org/0000-0002-9435-7750
김원우(Kim, Won Woo)
김지성(Kim, Ji Seong)
김현기(Kim, Hyunki) ORCID logo https://orcid.org/0000-0003-2292-5584
박수연(Park, Soo Yeon) ORCID logo https://orcid.org/0000-0003-3743-9554
성진실(Seong, Jin Sil) ORCID logo https://orcid.org/0000-0003-1794-5951
윤채옥(Yun, Chae Ok)
최일규(Choi, Il Kyu)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91080
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