Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells
Establishment and characterization of 5-fluorouracil-resistant gastric cancer cells
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DOI：
10.1016/s0304-3835(00)00535-8
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发表时间：
2000-10-16
期刊：
影响因子：
9.7
通讯作者：
Yoo, YD
中科院分区：
文献类型：
--
作者：
Chung, YM;Park, SH;Yoo, YD
用浓度递增的5-FU孵育韩国人胃癌细胞系，建立了2株5-FU耐药细胞系。由此产生的细胞株对5-FU的耐药性增加了800倍以上。通过逆转录聚合酶链式反应(RT-PCR)检测5-FU代谢相关基因的表达，探讨5-FU耐药的机制。OPRT、TP和UP在这些细胞中的表达显著下调，导致5-FU在核酸中的掺入量较低。相反，胸苷激酶(TK)在5-FU耐药细胞中的表达增加。这些结果有力地表明，阻止5-FU掺入核酸和TK的过度表达可能在这些细胞对5-FU的耐药性中起主要作用。有趣的是，这些细胞株对紫杉醇、顺铂和阿霉素表现出交叉耐药。提示热休克蛋白27和锰超氧化物歧化酶等其他因素也可能参与了这些细胞株多药耐药的机制。(C)2000爱思唯尔爱尔兰科学有限公司。保留所有权利。
Two 5-fluorouracil (5-FU)-resistant cell lines from a Korean gastric cancer cell line were established by incubation of the cells with increasing concentration of 5-FU. and the resultant cell lines showed an over 800-fold increased resistance to 5-FU. To identify the mechanism of 5-FU resistance, the expressions of genes involved in 5-FU metabolism were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). Expressions of orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and uridine phosphorylase (UP) were significantly downregulated in these cell lines, resulting in low incorporation of 5-FU into nucleic acids. In contrast, an increased expression of thymidine kinase (TK) was observed in 5-FU resistant cells. These results strongly indicate that blocking of 5-FU incorporation into nucleic acids and TK overexpression may play a major role in 5-FU resistance in these cells. Interestingly, these cell lines showed cross-resistance to paclitaxel, cisplatin, and doxorubicin. suggesting that other factors such as HSP27 and Mn-SOD could be also involved in the mechanism of multidrug resistance in these cell lines. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.