Abstract
It is unclear whether a subunit of glutamate cysteine ligase [a modifier subunit (GCLM) and a catalytic subunit (GCLC)] is an effective target for ameliorating cisplatin (CDDP)-resistance. We inhibited each subunit of GCL mRNA using a specific ribozyme (M-Rz and C-Rz) in the pulmonary adenocarcinoma cell line A549. GCL activity was suppressed by the ribozyme. CDDP-resistance was more effectively ameliorated when GCLM rather than GCLC was inhibited. GCLM is a potentially more effective pharmacologic target for ameliorating CDDP-resistance in non-small cell lung cancer than GCLC.
MeSH terms
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Antineoplastic Agents / pharmacology
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Base Sequence
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Blotting, Northern
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Carcinoma, Non-Small-Cell Lung / pathology
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Catalytic Domain
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Cell Line, Tumor
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Cell Survival
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Cisplatin / pharmacology*
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Dose-Response Relationship, Drug
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Drug Resistance, Neoplasm*
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Glutamate-Cysteine Ligase / chemistry*
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Glutathione / metabolism
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Humans
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Immunoblotting
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Lung Neoplasms / pathology*
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Molecular Sequence Data
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Nucleic Acid Conformation
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Plasmids / metabolism
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RNA, Catalytic / chemistry
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Tumor Suppressor Protein p53 / metabolism
Substances
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Antineoplastic Agents
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RNA, Catalytic
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RNA, Messenger
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Tumor Suppressor Protein p53
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Glutamate-Cysteine Ligase
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Glutathione
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Cisplatin