Abstract
The present study indicated that the combination of TRAIL/Apo-2L and CA-4 exerted synergistic anti-proliferative effect against human colon carcinoma cells including SW-620 and HCT-116 in vitro. Moreover, the increased anti-tumor efficacy of TRAIL/Apo-2L combined with CA-4 was further validated on SW-620 xenograft model in nude mice. These enhanced anti-cancer activities were accompanied by caspase-mediated apoptosis. Furthermore, it was identified that NF-κB as the major determinant of TRAIL/Apo-2L resistance could be blocked in cytoplasm by TRAIL/Apo-2L plus CA-4 treatment. Taken together, these findings build the rationale for further (pre)clinical development of TRAIL/Apo-2L and CA-4 against colorectal cancer.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Apoptosis / drug effects*
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Caspases / metabolism
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Cell Line, Tumor
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Cell Survival / drug effects
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / pathology
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Dose-Response Relationship, Drug
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Drug Synergism
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HCT116 Cells
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Humans
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Immunoblotting
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Mice
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Mice, Nude
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NF-kappa B / metabolism
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Poly(ADP-ribose) Polymerases / metabolism
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Protein Transport / drug effects
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Stilbenes / administration & dosage
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Stilbenes / pharmacology*
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TNF-Related Apoptosis-Inducing Ligand / administration & dosage
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TNF-Related Apoptosis-Inducing Ligand / pharmacology*
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Xenograft Model Antitumor Assays
Substances
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NF-kappa B
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Stilbenes
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TNF-Related Apoptosis-Inducing Ligand
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Poly(ADP-ribose) Polymerases
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Caspases
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fosbretabulin