The utility of an anti-fos ribozyme in reversing cisplatin resistance in human carcinomas.
The results presented here demonstrate that expression of a fos ribozyme limits Fos protein synthesis and enhances sensitivity of A2780DDP cells to antineoplastic agents, including cisplatin. Moreover, the reversal of this resistance is associated with down-regulation of dTMP synthase, DNA polymerase beta, topoisomerase I and hMTII-A, genes previously linked to DNA synthesis and repair. Thus these studies further implicate the role of the c-fos gene in DNA synthesis through modulation of expression of dTMP syntase, DNA polymerase beta and topoisomerase I. Finally, the use of ribozymes to circumvent drug resistance suggests their potential utility as agents to inhibit tumor cell growth.
Funato
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Department of Medical Oncology, City of Hope National Medical Center, Durate, CA 91010.
Yoshida
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E
Jiao
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Tone
T
T
Kashani-Sabet
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M
Scanlon
K J
KJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D002277:Carcinoma / Q000188:drug therapy; D002945:Cisplatin / Q000494:pharmacology*; D004351:Drug Resistance; D005069:Evaluation Studies as Topic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D016337:RNA, Catalytic / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D016760:Proto-Oncogene Proteins c-fos; D016337:RNA, Catalytic; D002945:Cisplatin