[Circumventing drug resistance in human tumors by antisense ribozyme].
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 hMT II-A, which are 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 synthase, 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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Dept. of Clinical Laboratory and Medicine, Tohoku University School of Medicine.
D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair; D004351:Drug Resistance; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology; D016372:RNA, Antisense / Q000494:pharmacology*; D016337:RNA, Catalytic / Q000494:pharmacology*; D013940:Thymidylate Synthase / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D016372:RNA, Antisense; D016337:RNA, Catalytic; D004247:DNA; D013940:Thymidylate Synthase; D002945:Cisplatin