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Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway

Hepatoma cells are known to be highly resistant to chemotherapy. Previously, we have found differential Taxol resistance in human and murine hepatoma cells. The aim of this study was to examine the effect of a multidrug resistance inhibitor, cyclosporin A in combination with Taxol on hepatoma in vit...

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Autores principales: Lin, H-L, Lui, W-Y, Liu, T-Y, Chi, C-W
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377082/
https://www.ncbi.nlm.nih.gov/pubmed/12644839
http://dx.doi.org/10.1038/sj.bjc.6600788
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author Lin, H-L
Lui, W-Y
Liu, T-Y
Chi, C-W
author_facet Lin, H-L
Lui, W-Y
Liu, T-Y
Chi, C-W
author_sort Lin, H-L
collection PubMed
description Hepatoma cells are known to be highly resistant to chemotherapy. Previously, we have found differential Taxol resistance in human and murine hepatoma cells. The aim of this study was to examine the effect of a multidrug resistance inhibitor, cyclosporin A in combination with Taxol on hepatoma in vitro and in vivo, and to identify the possible mechanism involved in Taxol resistance. Simultaneous treatment of cyclosporin A (0–10 μM) and Taxol (0.1 μM) inhibited cell growth in vitro. Cyclosporin A interfered with Taxol (0.1 μM)-induced AKT activation and BAD phosphorylation. Cyclosporin A combined with Taxol treatment augments caspase-9, -3 activation and loss of mitochondrial membrane potential in HepG2 cells. PI3 kinase inhibitor, wortmannin, or a dominant-negative AKT1 expression vector treatment partially enhanced Taxol-induced apoptosis indicating that PI3 kinase-AKT pathway was involved in Taxol-resistance pathway. Moreover, combination treatment reduced tumour growth in SCID and C57BL/6 mice as compared to either Taxol or cyclosporin A treatment. Our results indicate that the combination of cyclosporin A and Taxol is effective in the reversal of Taxol resistance through the inhibition of PI3 kinase-AKT1 pathway.
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spelling pubmed-23770822009-09-10 Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway Lin, H-L Lui, W-Y Liu, T-Y Chi, C-W Br J Cancer Experimental Therapeutics Hepatoma cells are known to be highly resistant to chemotherapy. Previously, we have found differential Taxol resistance in human and murine hepatoma cells. The aim of this study was to examine the effect of a multidrug resistance inhibitor, cyclosporin A in combination with Taxol on hepatoma in vitro and in vivo, and to identify the possible mechanism involved in Taxol resistance. Simultaneous treatment of cyclosporin A (0–10 μM) and Taxol (0.1 μM) inhibited cell growth in vitro. Cyclosporin A interfered with Taxol (0.1 μM)-induced AKT activation and BAD phosphorylation. Cyclosporin A combined with Taxol treatment augments caspase-9, -3 activation and loss of mitochondrial membrane potential in HepG2 cells. PI3 kinase inhibitor, wortmannin, or a dominant-negative AKT1 expression vector treatment partially enhanced Taxol-induced apoptosis indicating that PI3 kinase-AKT pathway was involved in Taxol-resistance pathway. Moreover, combination treatment reduced tumour growth in SCID and C57BL/6 mice as compared to either Taxol or cyclosporin A treatment. Our results indicate that the combination of cyclosporin A and Taxol is effective in the reversal of Taxol resistance through the inhibition of PI3 kinase-AKT1 pathway. Nature Publishing Group 2003-03-24 2003-03-18 /pmc/articles/PMC2377082/ /pubmed/12644839 http://dx.doi.org/10.1038/sj.bjc.6600788 Text en Copyright © 2003 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Experimental Therapeutics
Lin, H-L
Lui, W-Y
Liu, T-Y
Chi, C-W
Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway
title Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway
title_full Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway
title_fullStr Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway
title_full_unstemmed Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway
title_short Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway
title_sort reversal of taxol resistance in hepatoma by cyclosporin a: involvement of the pi-3 kinase-akt 1 pathway
topic Experimental Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377082/
https://www.ncbi.nlm.nih.gov/pubmed/12644839
http://dx.doi.org/10.1038/sj.bjc.6600788
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