Reversal of cisplatin resistance in vivo by an anti-fos ribozyme.
Human colon cancer cells, SW480DDP and SW620DDP, which express fos gene highly, are resistant to cisplatin treatment. We prepared a hammerhead ribozyme to selectively cleave fos mRNA and revealed that the for ribozyme significantly suppressed the expression of fos gene in resistant cells in vitro. The fos ribozyme which was transfected into the implanted tumor cells resistant to cisplatin, had also the ability to reduce the expression of fos gene in vivo, and reversed cell sensitivity to cisplatin. These results reinforce the potential role of anti-oncogene ribozymes in dealing with the problem of drug resistance, with new possible implications for gene targeting therapy.
Funato
T
T
Department of Clinical and Laboratory Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ishii
T
T
Kanbe
M
M
Scanlon
K J
KJ
Sasaki
T
T
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D016760:Proto-Oncogene Proteins c-fos; D016337:RNA, Catalytic; D012333:RNA, Messenger; D002945:Cisplatin