title: The modifier subunit of glutamate cysteine ligase (GCLM) is a molecular target for amelioration of cisplatin resistance in lung cancer.
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.
authors.affiliation: Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Masashi
authors.initials: M
authors.lastname: Tomisawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Abe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suemizu
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukamoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Tomii
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kawamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kijima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hatanaka
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Ueyama
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Koichi
authors.initials: K
authors.lastname: Kobayashi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D015152:Blotting, Northern; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005721:Glutamate-Cysteine Ligase / Q000737:chemistry*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000473:pathology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016337:RNA, Catalytic; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D002945:Cisplatin