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Cancer Chemotherapy and Pharmacology

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01.03.2012 | Original Article

ABT-263 sensitizes TRAIL-resistant hepatocarcinoma cells by downregulating the Bcl-2 family of anti-apoptotic protein

verfasst von: Guan Wang, Yao Zhan, Haiqing Wang, Wenhua Li

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 3/2012

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Abstract

Purpose

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its selective cytotoxicity to transformed cells. However, most human hepatocellular carcinomas (HCC) develop resistance to TRAIL. Thus, there is an urgent need to investigate the molecular targets and the underlying mechanisms that may be involved in overriding the resistance of tumor cells to TRAIL.

Methods

Cell viability analysis was performed in HCC cells after treatment with TRAIL and/or ABT-263. Flow cytometry was used to assess apoptosis. The expression of caspases and members of the Bcl-2 family was examined through immunoblot analysis. Finally, the viability of cancer cells transfected with a plasmid containing HBx (hepatitis B virus X protein) following treatment with TRAIL was also measured.

Results

In this study, we demonstrate that ABT-263, a potent and orally bioavailable inhibitor of the Bcl-2 family, was able to reverse the resistance of hepatocarcinoma cell lines to TRAIL-induced apoptosis, while sparing normal liver cells. The molecular mechanism of the reversal in resistance may be attributed to the inhibition by ABT-263 of anti-apoptosis proteins of the Bcl-2 family. In addition, we determined that HBx was able to sensitize TRAIL-resistant hepatocarcinoma Huh7 cells.

Conclusions

These findings provide a novel insight into the clinical application of TRAIL-induced apoptosis of HCC cells.

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Titel: ABT-263 sensitizes TRAIL-resistant hepatocarcinoma cells by downregulating the Bcl-2 family of anti-apoptotic protein
verfasst von: Guan Wang
Yao Zhan
Haiqing Wang
Wenhua Li
Publikationsdatum: 01.03.2012
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 3/2012
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-011-1763-0

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Springer Medizin

ABT-263 sensitizes TRAIL-resistant hepatocarcinoma cells by downregulating the Bcl-2 family of anti-apoptotic protein

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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