The modifier subunit of glutamate cysteine ligase (GCLM) is a molecular target for amelioration of cisplatin resistance in lung cancer.
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.
Inoue
Yoshimasa
Y
Department of Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
Tomisawa
Masashi
M
Yamazaki
Hitoshi
H
Abe
Yoshiyuki
Y
Suemizu
Hiroshi
H
Tsukamoto
Hideo
H
Tomii
Yasushi
Y
Kawamura
Masafumi
M
Kijima
Hiroshi
H
Hatanaka
Hiroyuki
H
Ueyama
Yoshito
Y
Nakamura
Masato
M
Kobayashi
Koichi
K
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
D000970:Antineoplastic Agents; D016337:RNA, Catalytic; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D002945:Cisplatin