Funato T, Yoshida E, Jiao L, Tone T, Kashani-Sabet M, Scanlon K J
Department of Medical Oncology, City of Hope National Medical Center, Durate, CA 91010.
Adv Enzyme Regul. 1992;32:195-209. doi: 10.1016/0065-2571(92)90017-t.
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.
此处呈现的结果表明，fos核酶的表达可限制Fos蛋白的合成，并增强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hMTII - 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合成中发挥作用。最后，使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的效用。
