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Sub-dose combination of R406 and ABT-263 enhances senolysis via ROS generation

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Title
Sub-dose combination of R406 and ABT-263 enhances senolysis via ROS generation
Alternative Title
활성산소종(ROS) 생성을 통한 R406 및 ABT-263 저용량 병용의 향상된 노화세포 제거 효과
DGIST Authors
Ahyeon YunYoung-Sam LeeYun-Il Lee
Advisor
이영삼
Co-Advisor(s)
Yun-Il Lee
Issued Date
2025
Awarded Date
2025-08-01
Type
Thesis
Description
Aging, Cellular senescence, Senolytics, Synergism, FAK, Bcl-2
Table Of Contents
List of Contents

Abstract i
List of contents ii-ⅲ
List of figures vi

Ⅰ. Introduction
1.1. Aging and Cellular Senescence 1
1.2. Age-related Diseases Associated With Cellular Senescence 2
1.3. Senotherapies: Senolytics and Senomorphics 3
1.4. Combination Therapy and Synergism 4
1.5. Synergyfinder: A Tool For Evaluating Synergistic Effect 5
1.6. R406 6
1.7. ABT-263 7
1.8. Overview of This Study 8

Ⅱ. Experimental Method & Materials
2.1. Cell Culture 9
2.2. Drug preparation 9
2.3. Cell viability assay 10
2.4. Flow cytometry 10
2.5. Synergyfinder 10
2.6. Western blot 11
2.7. ROS assay 11
2.8. Animals 12
2.9. Immunohistochemical staining 12
2.10. Statistical analyses 13

Ⅲ. Results
3.1.Identification of R406 and ABT-263 as a novel senolytic combination 14
3.2.In vitro Synergy Analysis of R406 and ABT-263 for Senolytic effect 17
3.3.Non-apoptotic cell death by sub-dose co-treatment of R406 and ABT-263 26
3.4.ROS-mediated senolysis by the combination of R406 and ABT-263 29
3.5.In vivo evaluation in a bleomycin-induced pulmonary fibrosis model 35

Ⅳ. Discussion
43

Ⅴ. Conclusion
46

Ⅵ. References
47

요 약 문
53
URI
https://scholar.dgist.ac.kr/handle/20.500.11750/59818
http://dgist.dcollection.net/common/orgView/200000889847
DOI
10.22677/THESIS.200000889847
Degree
Master
Department
Department of New Biology
Publisher
DGIST
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