목차

ABSTRACT i
TABLE OF CONTENTS iii
LIST OF FIGURES v
PART ONE
I. INTRODUCTION 1
II. MATERIALS AND METHODS 4
A. Cell line and reagents 4
B. Cell proliferation assay 4
C.Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay 4
D. Flow cytometric detection of apoptotic cells 5
E. Transfection of NAG-1 cDNA and siRNA 5
F. RT-PCR 5
G. Western blot analysis 6
H. Luciferase reporter assay 6
I. Caspase-3 activity assay 6
J. Animal study 7
K. Statistical analysis 7
III. RESULTS 8
A. Effects of EGCG and other catechins on growth and apoptosis of HNSCC cells 8
B. EGCG induces NAG-1 expression in time- and dose-dependent manner in HNSCC cells 10
C. Overexpression of NAG-1 promotes EGCG-induced apoptosis 13
D. Suppression of NAG-1 expression by siRNA desensitizes EGCG responses 16
E. EGCG induces NAG-1 expression through ATM-dependent p53 protein 19
F. Effect of EGCG on tumorigenicity and apoptosis in syngenic mouse model 24
IV. DISCUSSION 27
V. CONCLUSION 29
PART TWO
I. INTRODUCTION 30
II. MATERIALS AND METHODS 32
A. Cell lines and reagents 32
B. Cell proliferation assay 32
C. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end lebeling (TUNEL) assay 32
D. Mitochondrial membrane potential ( MMP ) assay 33
E. Transfection of NAG-1 cDNA and RNA interference ( RNAi ) 33
F. Western blot analysis 33
G. Animal study 34
H. Statistical analysis 34
III. RESULTS 35
A. Induction of NAG-1 and apoptosis in HNSCC cells by various NSAIDs 35
B. Overexpression and suppression of NAG-1 promotes and attenuates TA-induced apoptosis, respectively 42
C. Effect of TA on tumorigenicity and apoptosis in BALB/c nu/nu mice 47
IV. DISCUSSION 50
V. CONCLUSION 53
REFERENCES 54
국문요약 62