Combination of Radiotherapy and Adenovirus-Mediated p53 Gene Therapy for MDM2-Overexpressing Hepatocellular Carcinoma
スポンサーリンク
概要
- 論文の詳細を見る
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.
著者
-
Koom Woong
Department Of Radiation Oncology Brain Korea 21 Project For Medical Science Yonsei University Health
-
Kim Wonwoo
Department Of Radiation Oncology Brain Korea 21 Project For Medicine Yonsei University
-
Seong Jinsil
Department Of Radiation Oncology : Brain Korea 21 Project For Medical Science : Institute For Gastro
-
Kim Hyunki
Department Of Pathology And Bk21 Project For Medical Science Yonsei University College Of Medicine
-
PARK Soo-Yeon
Brain Korea 21 Project for Medical Sciences, Institute for Cancer Research, Yonsei University College of Medicine
-
KIM Wonwoo
Brain Korea 21 Project for Medical Sciences, Institute for Cancer Research, Yonsei University College of Medicine
-
KIM Minjung
Brain Korea 21 Project for Medical Sciences, Institute for Cancer Research, Yonsei University College of Medicine
-
KIM Ji-Seong
Brain Korea 21 Project for Medical Sciences, Institute for Cancer Research, Yonsei University College of Medicine
-
CHOI Il-Kyu
Graduate Program for Nanomedical Science, Yonsei University
-
YUN Chae-Ok
Brain Korea 21 Project for Medical Sciences, Institute for Cancer Research, Yonsei University College of Medicine
-
SEONG Jinsil
Department of Radiation Oncology, Yonsei University College of Medicine
-
KIM Hyunki
Department of Pathology, Institute for Cancer Research, Yonsei Cancer Center, Yonsei University College of Medicine
-
KOOM Woong
Department of Radiation Oncology, Yonsei University College of Medicine
関連論文
- Recombinant Human Epidermal Growth Factor (rhEGF) Protects Radiation-Induced Intestine Injury in Murine System
- Identification of Proteins that Regulate Radiation-induced Apoptosis in Murine Tumors with Wild Type p53
- Enhancement of Tumor Radioresponse by Wortmannin in C3H/HeJ Hepatocarcinoma
- Clinical results of 3-dimensional conformal radiotherapy combined with transarterial chemoembolization for hepatocellular carcinoma in the cirrhotic patients
- Tudor Domain-Containing Protein 4 as a Potential Cancer/Testis Antigen in Liver Cancer
- Radiation-induced hepatic toxicity after radiotherapy combined with chemotherapy for hepatocellular carcinoma
- A Novel Combination Treatment of Armed Oncolytic Adenovirus Expressing IL-12 and GM-CSF with Radiotherapy in Murine Hepatocarcinoma
- A Novel Combination Treatment of Armed Oncolytic Adenovirus Expressing IL-12 and GM-CSF with Radiotherapy in Murine Hepatocarcinoma
- Combination of Radiotherapy and Adenovirus-Mediated p53 Gene Therapy for MDM2-Overexpressing Hepatocellular Carcinoma