Abstract
Overexpression of human epidermal growth factor receptor (EGFR) has been detected in various tumors and is associated with poor outcomes. Combination treatment regimens with EGFR-targeting and cytotoxic agents are a potential therapeutic option for rhabdomyosarcoma (RMS) with EGFR amplification. We investigated the effects of combination treatment with actinomycin D and the EGFR-targeting agent cetuximab in 4 RMS cell lines. All 4 RMS cell lines expressed wild-type K-ras, and 2 of the 4 overexpressed EGFR, as determined by flow cytometry, real-time PCR and direct sequencing. Combination of cetuximab and actinomycin D was highly effective, synergistically inhibiting cell growth with a combination index of less than 1. Moreover, combination treatment with these two reagents increased the rate of apoptosis in EGFR-positive cells. Cetuximab has antitumor activity in EGFR-amplified RMS cells when combined with antitumor reagents, indicating that cetuximab is a potential therapeutic reagent for RMS with EGFR amplification.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal, Humanized / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Apoptosis / drug effects*
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Blotting, Western
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Cell Proliferation / drug effects
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Cetuximab
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Dactinomycin / administration & dosage
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Drug Synergism*
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ErbB Receptors / genetics*
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ErbB Receptors / metabolism
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Flow Cytometry
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Gene Amplification*
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Humans
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In Vitro Techniques
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Mutation / genetics
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins p21(ras)
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Rhabdomyosarcoma / drug therapy*
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Rhabdomyosarcoma / genetics
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Rhabdomyosarcoma / pathology*
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Tumor Cells, Cultured
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ras Proteins / genetics
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ras Proteins / metabolism
Substances
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Antibodies, Monoclonal, Humanized
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KRAS protein, human
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Proto-Oncogene Proteins
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RNA, Messenger
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Dactinomycin
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EGFR protein, human
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ErbB Receptors
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Proto-Oncogene Proteins p21(ras)
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ras Proteins
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Cetuximab