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Aspirin과 TRAIL 병합처리시 자궁경부암인 HeLa cell에 미치는 영향
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Se Ran IM | - |
| dc.date.accessioned | 2019-10-21T07:17:35Z | - |
| dc.date.available | 2019-10-21T07:17:35Z | - |
| dc.date.issued | 2012-02 | - |
| dc.identifier.other | 12384 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/17869 | - |
| dc.description | 학위논문(석사)아주대학교 일반대학원 :의생명학과,2012. 2 | - |
| dc.description.tableofcontents | ABSTRACT ⅰ TABLE OF CONTENTS ⅲ LIST OF FIGURES ⅴ Ⅰ. INTRODUCTION 1 Ⅱ. MATERIALS AND METHODS 3 A. Reagents 3 B. Antibodies 3 C. Cell culture 3 D. Cell viability assay 3 E. Cytotoxicity assay 4 F. Sub G1 analyses 4 G. Annexin-V/ PI staining 4 H. Immunoblotting 5 I. Measurement of mitochondrial membrane potential 5 J. Analysis of cytochrome c release 6 Ⅲ. RESULTS 7 1. Aspirin inhibits the proliferation of HeLa cells and augments TRAIL-mediated cell death 7 2. Aspirin triggers TRAIL-induced apoptotic cell death via enhanced caspase activity 10 3. Aspirin results in TRAIL-induced caspase-dependent mitochondrial membrane potential change and cytochrome c release 16 4. Aspirin makes TRAIL-resistant HeLa cells TRAIL-sensitive through inhibition of ERK1/2 activation 19 Ⅳ. DISCUSSION 26 Ⅴ. REFERENCES 29 Ⅵ. 국문요약 36 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | Aspirin과 TRAIL 병합처리시 자궁경부암인 HeLa cell에 미치는 영향 | - |
| dc.title.alternative | Se-Ran IM | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | Se-Ran IM | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2012. 2 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 570100 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000012384 | - |
| dc.description.alternativeAbstract | Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family of cytokines and induces apoptosis in most tumor cells. Although TRAIL is considered a promising drug for cancer therapies because of its tumor selectivity, many tumors are resistant to TRAIL. Thus TRAIL-resistant cancer cells must be sensitized first to become responsive to TRAIL. In this study, I studied whether pretreatment by aspirin augmented TRAIL-induced apoptotic death in HeLa cells, which derived from cervical cancer and investigated the underlying mechanism. Methods: Cell viability and proliferation were assessed by MTT assay and cytotoxicity was analyzed by LDH assay. Annexin-V /PI staining and sub G1 analysis were used for evaluation of apoptotic cells. We measured mitochondrial membrane potential in HeLa cells undergoing apoptosis by using JC-1. Protein level changes were documented by western blot analysis. Results: Aspirin inhibited proliferation of HeLa cells in the time- and dose-dependent manners. The combined treatment of aspirin with TRAIL strongly enhanced TRAIL-induced apoptotic cell death in HeLa cells. It activated caspase-8, -9 and -3 and caused the caspase-dependent loss of MMP and the release of cytochrome c from mitochondria to cytosol. The apoptotic characteristics enhanced by the combined treatment were inhibited by a pan-caspase inhibitor z-VAD-fmk. Interestingly, TRAIL caused the activation of ERK, whereas the ERK activation was blocked by aspirin. As a result, the activation of ERK decreased and additionally, Mcl-1 also decreased in combination treatment. Conclusion: TRAIL in combination with aspirin significantly increase apoptosis in HeLa cells through caspase-and mitochondrial-dependent pathway. Mechanism of such a promoted apoptotic effect might be associated with that TRAIL-induced ERK activation which triggers survival signal to HeLa cells is blocked by pretreatment of aspirin. Inhibition of ERK activation enhances TRAIL-induced caspase activation, which rapidly cleavages Mcl-1. It could also trigger translocation of cleaved Bid to mitochondria to activate mitochondrial pathway, which also amplifies caspase activation. Eventually, pre-treated aspirin could block the survival signal and enhance caspase-and mitochondrial-dependent apoptotic cell death in HeLa cells treated with TRAIL. | - |
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- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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