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Human hepatocellular carcinoma cells resist to TRAIL-induced apoptosis, and the resistance is abolished by cisplatin

Authors
 Eui Cheol Shin  ;  Young Rim Seong  ;  Chul Hoon Kim  ;  , Hoguen Kim  ;  Young Soo Ahn  ;  Kunhong Kim  ;  Se Jong Kim  ;  Seung Suh Hong  ;  Jeon Han Park 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.34(2) : 114-122, 2002 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2002
MeSH
Apoptosis* ; Apoptosis Regulatory Proteins ; CASP8 and FADD-Like Apoptosis Regulating Protein ; Carcinoma, Hepatocellular/pathology* ; Carrier Proteins/genetics ; Cell Line ; Cisplatin/pharmacology* ; Cycloheximide/metabolism ; Humans ; Intracellular Signaling Peptides and Proteins* ; Membrane Glycoproteins/physiology* ; NF-kappa B/metabolism ; Peptides/metabolism ; Receptors, Tumor Necrosis Factor/genetics ; TNF-Related Apoptosis-Inducing Ligand ; Tumor Necrosis Factor-alpha/physiology*
Keywords
TRAIL ; apoptosis ; HCC ; cisplatin ; cycloheximide
Abstract
TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, selectively induce apoptosis in various transformed cell lines but not in almost-normal tissues. It is regulated by 2 death receptors, TRAIL receptor 1(TRAIL-R1) and TRAIL-R2 and 2 decoy receptors, TRAIL-R3 and TRAIL-R4. However, the determining factors of the sensitivity to TRAIL-induced apoptosis are not clearly understood. Herein, we investigated the expression of TRAIL-R, c-FLIP, FADD-like interleukin-1β-converting enzyme inhibitory protein, and TRAIL-induced apoptosis in human hepatocellular carcinoma (HCC) cell lines. Seven of ten HCC cell lines showed resistance to TRAIL-induced apoptosis and five of seven TRAIL-resistant cell lines became sensitive to TRAIL by co-treatment with cycloheximide. In HCC cell lines, their TRAIL resistance did not correlate with the basal expression level of TRAIL receptors or c-FLIP, however, in human tissues, TRAIL-R1 and TRAIL-R2 expressions were notably decreased compared to normal counterpart. Cisplatin showed synergistic effect on TRAIL-induced apoptosis in most HCC cell lines regardless of their p53 status and TRAIL-R1 was induced by cisplatin treatment in certain cell lines. Inhibition of nuclear factor K B (NF-κB) by SN50, a peptide inhibitor of NF-κB activity, had no effect on TRAIL-induced apoptosis in HCC cells. These results suggest that (a) the majority of human HCC cell lines are resistant to TRAIL-induced apoptosis and cycloheximide-sensitive short-lived antiapoptotic molecule(s) is responsible for this resistance, (b) the expression of TRAIL-R1 and TRAIL-R2 is reduced in HCC tissues, and the increased expression of TRAIL-R1 may be a mechanism of cisplatininduced sensitization to TRAIL-induced apoptosis in some HCC cells, and (c) the activation of NF-κB may not be involved in the TRAIL resistance of HCC cells.
Files in This Item:
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DOI
10.1038/emm.2002.17
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Kim, Se Jong(김세종)
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Kim, Ho Keun(김호근)
Park, Jeon Han(박전한) ORCID logo https://orcid.org/0000-0001-9604-3205
Ahn, Young Soo(안영수)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/143434
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