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[通过反义核酶规避人类肿瘤中的耐药性]

[Circumventing drug resistance in human tumors by antisense ribozyme].

作者信息

Funato T

机构信息

Dept. of Clinical Laboratory and Medicine, Tohoku University School of Medicine.

出版信息

Gan To Kagaku Ryoho. 1994 Feb;21(3):336-42.

PMID:8109989
Abstract

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.

摘要

此处呈现的结果表明,fos核酶的表达限制了Fos蛋白的合成,并增强了A2780DDP细胞对包括顺铂在内的抗肿瘤药物的敏感性。此外,这种耐药性的逆转与dTMP合酶、DNA聚合酶β、拓扑异构酶I和hMT II - A的下调有关,这些基因先前与DNA合成和修复相关。因此,这些研究进一步表明c - fos基因通过调节dTMP合酶、DNA聚合酶β和拓扑异构酶I的表达在DNA合成中所起的作用。最后,利用核酶来克服耐药性表明它们作为抑制肿瘤细胞生长的药物具有潜在用途。

相似文献

1
[Circumventing drug resistance in human tumors by antisense ribozyme].[通过反义核酶规避人类肿瘤中的耐药性]
Gan To Kagaku Ryoho. 1994 Feb;21(3):336-42.
2
The utility of an anti-fos ribozyme in reversing cisplatin resistance in human carcinomas.一种抗Fos核酶在逆转人类癌症顺铂耐药性中的作用。
Adv Enzyme Regul. 1992;32:195-209. doi: 10.1016/0065-2571(92)90017-t.
3
Ribozyme-mediated cleavage of c-fos mRNA reduces gene expression of DNA synthesis enzymes and metallothionein.核酶介导的c-fos信使核糖核酸切割可降低DNA合成酶和金属硫蛋白的基因表达。
Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10591-5. doi: 10.1073/pnas.88.23.10591.
4
Reversal of cisplatin resistance in vivo by an anti-fos ribozyme.抗Fos核酶在体内逆转顺铂耐药性
In Vivo. 1997 May-Jun;11(3):217-20.
5
[Reversal of drug resistance in human cancer cells by anti-oncogenes].
Gan To Kagaku Ryoho. 1997 Feb;24(4):395-400.
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[Circumventing multidrug resistance in human cancer by anti-ribozyme].
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SKY1 is involved in cisplatin-induced cell kill in Saccharomyces cerevisiae, and inactivation of its human homologue, SRPK1, induces cisplatin resistance in a human ovarian carcinoma cell line.SKY1参与酿酒酵母中顺铂诱导的细胞杀伤,其人类同源物SRPK1的失活在人卵巢癌细胞系中诱导顺铂耐药。
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BRCA1 up-regulation is associated with repair-mediated resistance to cis-diamminedichloroplatinum(II).BRCA1基因上调与顺二氯二氨合铂(II)修复介导的耐药性相关。
Cancer Res. 1998 Mar 15;58(6):1120-3.
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Detection of drug resistance in human tumors by in vitro enzymatic amplification.通过体外酶促扩增检测人类肿瘤中的耐药性。
Cancer Res. 1988 Oct 15;48(20):5775-8.
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Enhanced cisplatin cytotoxicity by disturbing the nucleotide excision repair pathway in ovarian cancer cell lines.通过干扰卵巢癌细胞系中的核苷酸切除修复途径增强顺铂细胞毒性。
Cancer Res. 2003 Mar 15;63(6):1311-6.

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Br J Cancer. 1996 Aug;74(3):387-93. doi: 10.1038/bjc.1996.370.