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Targeting Peroxiredoxins enhances anticancer drug effects by suppressing stemness properties

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Author(s)
Thummudune Appuhamillage Nisansala Chandimali
Issued Date
2020
URI
http://dcoll.jejunu.ac.kr/common/orgView/000000009355
Abstract
약초식물에서추출한다른천연식물추출물은암진행의기본메커니즘을이해하고약물에대한내성을 이해함으로써이러한도전을극복함으로써대장암의성공적인임상관리에대한새로운통찰력을제공 할수있기때문에여러유형의암에대한성공적인치료전략으로서세계적으로주목을받고있습니다. 따라서, 먼저천연식물추출물중하나인Shikonin이 mTOR 신호전달을억제함으로써결장암세포아 pop 토시스를유도하고 Prx V의과발현은 mTOR 신호전달을조절함으로써Shikonin의아 pop 토시스 -유도효과를제거할수있다고결론지었다. 비록 Prx V의이러한효과가향후연구에서심층적으로연구 될필요가있지만, 우리의결과는대장암세포의표적화에있어대장암의더나은임상관리를가능하게할 수있는기저메커니즘을이해하는새로운통찰력을제공합니다. 또한, 우리는 A549 / GR CSCs의 stemness 속성 Prx II의 overexpression에의해결정적으로영향을받 을수있습니다요약. 또한, miR-122는 Prx II를직접표적화함으로써 Prx II에의해유도된줄기특성을 제거할수있다. 따라서, miR-122를회복시키는접근법은 NSCLC의치료관리에효과적일수있다
Different natural plant extracts, extracted from herbal plants, are gaining global attention as successful therapeutic strategies for several types of cancers as Understanding the underlying mechanisms of cancer progression and resistance to drugs may provide new insights into successful clinical management of colon cancers by overcoming this challenge. Therefore, first we concluded that Shikonin, one of natural plant extracts, induces colon cancer cell apoptosis by inhibiting mTOR signaling and overexpression of Prx V can abrogate the apoptosis-inducing effects of Shikonin by regulating mTOR signaling. Even though these effects of Prx V need to be studied deeply in detail in future studies, our results provide new insight into understanding the underlying mechanisms which may allow advantage in targeting colon cancer cellsfor abetter clinical management of colon cancer. Also, we summarized that stemness properties of A549/GR CSCs can be critically affected by the overexpression of Prx II. Also, miR-122 can abolish the stemness characteristics induced by Prx II by directly targeting Prx II. Thus, the approaches to restore miR-122 may effective for therapeutic management of NSCLCs
Affiliation
제주대학교 대학원
Department
대학원 차세대융복합과학기술협동과정
Advisor
Lee, Dong Sun
Awarded Date
2020. 2
Table Of Contents
LIST OF FIGURES 1
SUMMARY 2
초록. 3
1. CHAPTER 1 4
1.1 ABSTRACT. 4
1.2. INTRODUCTION 5
1.3. MATERIALS AND METHODS 6
1.3.1. CREATION OF REQUIRED STABLE CELL LINES AND MAINTENANCE . 6
1.3.2. APOPTOSIS ASSAY AND CELL VIABILITY ASSAY. 6
1.3.3.WESTERN BLOTTING. 6
1.3.4. DCF-DA, DHE AND JC-1STAINING ASSAYS 7
1.3.5. TRANSWELL ASSAYS 7
1.3.6. IMMUNOCYTOCHEMISTRY 8
1.3.7. COLONY-FORMATION ASSAY 8
1.3.8. SPHERE-FORMATION ASSAY 9
1.3.9. STATISTICAL ANALYSIS 9
1.4. RESULTS. 10
1.4.1. SHIKONIN DOWN REGULATES THE MALIGNANCY AND PROLIFERATION OF COLON CANCER CELLS 10
1.4.2. SHIKONIN CONTROLS THE OXIDATIVE STATE AND ANTIOXIDANT ENZYME SYSTEM OF COLON CANCER CELLS. 13
1.4.3. MTOR SIGNALING IN COLON CANCER CELLS IS REGULATED BY SHIKONIN 15
1.5. DISCUSSION. 20
1.6. CONCLUSION 22
2. CHAPTER 2. 23
2.1. ABSTRACT 23
2.2. INTRODUCTION 24
2.3. MATERIALS AND METHODS. 26
2.3.1. CELL CULTURE, GENERATING STABLE CELL LINES AND TRANSFECTIONS 26
2.3.2. CELL PROLIFERATION AND APOPTOSIS ASSAYS 26
2.3.3. WESTERN BLOT ANALYSIS. 26
2.3.4. DCF-DA ASSAY. 27
2.3.5. TRANSWELL ASSAYS. 27
2.3.6. SPHERE-FORMATION AND ICC ASSAYS 28
2.3.7. ICC ASSAY 28
2.3.8. COLONY-FORMATION ASSAY 28
2.3.9. XENOGRAFT MODEL AND OPTICAL IMAGING 29
2.3.10. DATA ANALYSIS 29
2.4. RESULTS 30
2.4.1. PRX II MEDIATES GR NSCLC CELL STEMNESS 30
2.4.2. A549/ GR CD133+ CELLS SHOWED HIGHER EXPRESSION OF PRX II AND STEMNESS CHARACTERISTICS 32
2.4.3. KNOCKDOWN OF PRX II WEAKENS THE STEM-CELL RELATED CHARACTERISTICS IN A549/GR CSCS . 34
2.4.4. TRANSFECTION OF MIR-122 SUPPRESSES STEM CELL-LIKE CHARACTERISTICS IN A549/ GR CSCS BY PRX II INHIBITION 36
2.4.5. MIR-122 TRANSFECTION INHIBITS TUMOR GROWTH IN VIVO THROUGH THE INHIBITION OF PRX II 38 2.5. DISCUSSION 40
2.6. CONCLUSION 42
3. REFERENCES 43
Degree
Master
Publisher
제주대학교 대학원
Citation
Thummudune Appuhamillage Nisansala Chandimali. (2020). Targeting Peroxiredoxins enhances anticancer drug effects by suppressing stemness properties
Type
Dissertation
Appears in Collections:
General Graduate School > Interdisciplinary Graduate Program in Advanced Convergence Technology and Science
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