High expression of thymidylate synthase leads to resistance to 5-fluorouracil in biliary tract carcinoma in vitro.

High expression of thymidylate synthase leads to resistance to 5-fluorouracil in biliary tract carcinoma in vitro.
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DOI:
10.1111/j.1349-7006.2001.tb01068.x
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发表时间:
2001-10
期刊:
Japanese journal of cancer research : Gann
影响因子:
--
通讯作者:
Kuroda Y
Kuroda Y
中科院分区:
其他
文献类型:
--
作者:
Habara K;Ajiki T;Kamigaki T;Nakamura T;Kuroda Y

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为了评价5‐氟尿嘧啶(5‐FU)化疗对人胆道癌的影响,我们在体外比较了4种人胆道癌细胞和12种不同人体器官消化癌细胞的5‐FU敏感性、胸腺嘧啶合成酶(TS)含量和二氢嘧啶脱氢酶(DPD)活性。用MTT法分析5‐FU在细胞系中的敏感性。用[6‐3H]FdUMP结合法分析TS含量,用薄层色谱(TLC)分析DPD活性。胆道癌细胞系的5‐FU lC50值显著高于其他消化器官癌细胞系,分别为97、45、119和194,高于其他消化、胰腺、结肠和胃癌细胞系的浓度。胆道癌细胞系TS含量也显著高于其他脏器癌细胞系。然而,在每个器官的癌细胞系之间,DPD活性没有差异。细胞系中TS含量与5‐FU敏感性显著相关,但DPD活性与5‐FU敏感性无关。因此,在本研究中,与其他消化器官的肿瘤相比,TS的表达影响了胆道癌对5 - FU的高耐药性。
To evaluate the effect of chemotherapy of 5‐fluorouracil (5‐FU) in human biliary tract carcinoma, we studied 5‐FU sensitivity, thymidylate synthase (TS) content, and dihydropyrimidine dehydroge‐nase (DPD) activity in 4 human biliary tract carcinoma cell lines compared to 12 various digestive carcinoma cell lines of human organs in vitro. 5‐FU sensitivity in the cell lines was analyzed by MTT assay. TS content was analyzed by the [6‐3H]FdUMP binding assay method, and DPD activity was analyzed by thin‐layer chromatography (TLC). 5‐FU lC50 values of biliary tract carcinoma cell lines were significantly higher than those of the carcinoma cell lines of the other digestive organs: 97, 45, 119, and 194 tunes the concentration of the other digestive, pancreas, colon, and gastric carcinoma cell lines, respectively. TS content of biliary tract carcinoma cell lines was also significantly greater than that of the carcinoma cell lines of the other organs. No difference in DPD activity, however, was recognized between the carcinoma cell lines of each organ. TS content in the cell lines significantly correlated with 5‐FU sensitivity, but DPD activity did not. Therefore, in the present study, TS expression was concluded to influence the high resistance to 5‐FU of biliary tract carcinoma in comparison with the carcinomas of the other digestive organs.
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发表时间: 1995-06-01
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期刊: Japanese journal of cancer research : Gann
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