Abstract
To increase the efficacy of currently used anti-cancer genotoxins, a combination use of different drugs is a potential new therapeutical tool. Here, we reported that a synthetic RasGAP-derived peptide 38GAP with RasGAP(301-326) and TAT penetration sequences could enhance the effect of chemotherapeutic agent CDDP in human colon carcinoma HCT116 cells. Our results showed that 38GAP significantly increased the CDDP-induced apoptosis in HCT116 cells. This synergistic effect was associated with abrogation of CDDP-induced G2/M arrest by down-regulations of phospho-Cdc2 and p21, and inhibitions of phospho-AKT, phospho-ERK and NF-κB. In animal models, 38GAP combined with CDDP significantly suppressed CT26 tumor growth, while 38GAP alone showed slight inhibitory effect. Our data suggest that 38GAP in combination with chemotherapeutics will become a potential therapeutic strategy for colon cancers.
Copyright © 2011 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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Amino Acid Sequence
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Animals
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Apoptosis / drug effects
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Cell Growth Processes / drug effects
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Cisplatin / pharmacology*
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Colonic Neoplasms / drug therapy*
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism*
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Colonic Neoplasms / pathology
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DNA Damage
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Down-Regulation / drug effects
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Drug Synergism
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Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
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Extracellular Signal-Regulated MAP Kinases / metabolism
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GTPase-Activating Proteins / pharmacology*
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HCT116 Cells
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Humans
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Male
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Mice
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Mice, Inbred BALB C
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Molecular Sequence Data
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Peptide Fragments / pharmacology*
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Proto-Oncogene Proteins c-akt / antagonists & inhibitors
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Proto-Oncogene Proteins c-akt / metabolism
Substances
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GTPase-Activating Proteins
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NF-kappa B
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Peptide Fragments
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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Cisplatin