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독소루비신 내성 백혈병세포에서 방사선 내성에 대한 분자기전

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Author(s)
강성인
Issued Date
2006
Abstract
This study investigated radioresistance mechanisms in the doxorubicin-resistant acute myelogenous leukemia (AML-2/DX100) cells. AML-2/DX100 cells also showed resistance to radiation. In AML-2/WT cells, radiation increased ratio of Bax/Bcl-2 expression and its translocation to mitochondria, consequently induced the release of cytochrome c from the mitochondria with the subsequent caspase-3 activation. On the contrary, in AML-2/DX100 cells, radiation neither increased Bax/Bcl-2 expression ratio nor its translocation to mitochondria. A specific p38 inhibitor SB203580 increased radioresistance in AML-2/WT cells but little in AML-2/DX100 cells. It inhibited radiation-induced Bax translocation in AML-2/WT cells but not in AML-2/DX100 cells, indicating that p38 MAPK is working after irradiation in AML-2/WT cells but not in AML-2/DX100 cells. Electrophoretic mobility shift assay and Western blot analysis revealed that NF-κB in AML-2/DX100 cells was more activated with degradation of cytosolic IκBα than was that of AML-2/WT cells. cDNA microarray showed that Bfl-1/A1 and granzyme H in AML-2/DX100 were highly up-regulated (6.21-fold) and down-regulated (6.49-fold), respectively as compared with each of AML-2/WT cells, which were confirmed by RT-PCR assay.
Taken together, these results indicate that radioresistance mechanisms of AML-2/DX100 cells could be related to alterations in mitochondrial translocation of Bax and Bcl-2, and in expression of pro-apoptotic (granzyme H) and anti-apoptotic (Bfl-1/A1) genes. It has been shown that balance of p38 MAPK and NF-κB signals is a determinant in radiosensitivity of AML-2/WT cells and AML-2/DX100 cells.
Alternative Title
Molecular mechanism of radioresistance of the doxorubicin-resistant leukemic cell line
Alternative Author(s)
kang, sung in
Affiliation
조선대학교 대학원
Department
일반대학원 의학과
Advisor
최철희
Awarded Date
2007-02
Table Of Contents
Ⅰ 서론 = 1
Ⅱ 연구 재료 및 방법 = 3
1 세포 배양과 내성 세포주의 선별 = 3
2 세포 독성실험 = 4
3 RT-PCR 분석 = 4
4 Western blot 분석 = 6
5 미토콘드리아 단백질 추출 = 7
6 핵 단백질 추출 = 7
7 Electrophoretic mobility shift assay (EMSA) = 8
8 DNA chip = 8
Ⅲ 결과 = 11
1 내인성 ROS-scavenging capacity가 증가되어 있는 독소루비신 내성세포 AML-2/DX100 세포에서 방사선에 대한 교차내성 = 11
2 AML-2/DX100 세포에서 Bax의 미토콘드리아로의 translocation 변화 = 11
3 AML-2/WT와 AML-2/DX100세포사이에 방사선 감수성에 대한 MAPK 경로 = 11
4 AML-2/WT와 AML-2/DX100세포사이에 방사선 내성에 대한 NF-κB의 관여 = 12
5 cDNA microarray를 이용한 apoptosis에 관련된 유전자의 발현 양상의 측정 = 13
Ⅳ 고찰 = 25
Ⅴ 결론 = 30
Ⅵ 감사의 글 = 31
Ⅶ 참고 문헌 = 32
Degree
Doctor
Publisher
조선대학교 대학원
Citation
강성인. (2006). 독소루비신 내성 백혈병세포에서 방사선 내성에 대한 분자기전.
Type
Dissertation
URI
https://oak.chosun.ac.kr/handle/2020.oak/6590
http://chosun.dcollection.net/common/orgView/200000233995
Appears in Collections:
General Graduate School > 4. Theses(Ph.D)
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