Abstract
beta-tubulin (beta-TUB), Bcl-XL, and additionally glutathione S-transferase pi (GSTpi) were found to participate in sensitivity to docetaxel (TXT) in 7 human gastrointestinal cancer cell lines. The gene expression level of beta-TUB, Bcl-XL, and GSTpi was closely correlated with the IC50 for TXT. beta-TUB amount related to TXT resistance, and GST activity was correlated with IC50 for TXT in the 30-min treatment setting. Bcl-XL transfection increased TXT resistance of COLO201 cells, whereas GST inhibition by ethacrynic acid enhanced TXT cytotoxicity. Continuous TXT treatment increased beta-TUB and GSTpi expression, but the increased GSTpi mRNA was observed in TXT-resistant HCC-48 cells alone.
MeSH terms
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Cell Division / drug effects
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Docetaxel
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Ethacrynic Acid / pharmacology
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Flow Cytometry
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Gastrointestinal Neoplasms / drug therapy
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Gastrointestinal Neoplasms / enzymology
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Gastrointestinal Neoplasms / genetics*
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Gastrointestinal Neoplasms / pathology*
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Gene Expression Regulation, Neoplastic / drug effects*
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Genes, p53 / genetics
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Glutathione S-Transferase pi
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Glutathione Transferase / genetics
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Humans
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Inhibitory Concentration 50
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Isoenzymes / genetics
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Paclitaxel / administration & dosage
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Paclitaxel / analogs & derivatives*
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Paclitaxel / pharmacology*
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Paclitaxel / therapeutic use
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Proto-Oncogene Proteins c-bcl-2 / genetics
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Taxoids*
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Time Factors
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Transfection
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Tubulin / genetics
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Tumor Cells, Cultured
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bcl-X Protein
Substances
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BCL2L1 protein, human
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Isoenzymes
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Taxoids
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Tubulin
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bcl-X Protein
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Docetaxel
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GSTP1 protein, human
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Glutathione S-Transferase pi
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Glutathione Transferase
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Ethacrynic Acid
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Paclitaxel