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C3H/HeJ 마우스 간암에서 MEK 억제제에 의한 방사선 감수성 향상 효과

Other Titles
 Enhancement of Tumor Response by MEK Inhibitor in Murine HCa-I Tumors 
Authors
 김성희  ;  성진실 
Citation
 Journal of the Korean Society for Therapeutic Radiology and Oncology (대한방사선종양학회지), Vol.21(3) : 207-215, 2003 
Journal Title
 Journal of the Korean Society for Therapeutic Radiology and Oncology (대한방사선종양학회지) 
ISSN
 1229-8719 
Issue Date
2003
MeSH
PD98059 ; lonzing radiation ; apoptosis ; hepatocarcinoma
Keywords
PD98059 ; lonzing radiation ; apoptosis ; hepatocarcinoma
Abstract
Purpose: Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protin kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Materials and Methods: Murine hepatocarcinoma, Hca-I is known to be highly radioresistant with a TCD50(radiation dose yield in 50% cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case of radioresistant tumor. C3H/HeJ mice bearing 7.5~8 mm Hca-I, were treated with PD98059(intratumoral injection of 0.16㎍ in 50㎕). Results: Downregulation of ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to increase the effect of the tumor radioresponse with an enhancement factor(EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number of apoptotic nuclei in 1000 nuclei X100) was 1.2% in the case of radiation treatment alone, 0.9% in the case of drug treatment alone and 4.9%, 5.3% in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed upregulation of p53, p21(WAF1/CIP1) and Bcl-Xs in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as Bcl-XL, Bax and Bcl-2 were changed to a lesser extent. Conculsion: The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment.
Files in This Item:
T200305056.pdf Download
DOI
OAK-2003-00846
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers
Yonsei Authors
Seong, Jin Sil(성진실) ORCID logo https://orcid.org/0000-0003-1794-5951
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/114006
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