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背景与目的:氟尿嘧啶(5-FU)是胃肠道肿瘤化疗的首选和基本用药,其分解代谢的限速酶———二氢嘧啶脱氢酶(DPD)和激活酶———胸苷磷酸化酶(TP)决定了肿瘤区域的药物浓度和作用,且与5-FU的化疗敏感性有一定相关性。本研究旨在观察胃肠道肿瘤细胞中,5-FU对DPD和TP的表达有无调节作用。方法:选取胃癌细胞株SGC7901、大肠癌细胞株SW 1116和人脐静脉内皮细胞ECV-304,用不同浓度的5-FU作用不同时间后,以RT-PCR,ELISA和免疫组化等方法分别检测DPD和TP的mRNA和蛋白含量,观察药物作用对不同细胞代谢酶表达的影响。结果:5-FU作用于不同细胞后表现不同:其中SGC7901、SW 1116两株肿瘤细胞的DPD蛋白水平均上调,且表现为时间依赖性;在上述两株细胞中,TP蛋白表达呈小剂量上调、大剂量下调的双重效应,并随时间延长表达增加;5-FU作用后DPD和TP mRNA水平则无显著改变。ECV-304细胞株的DPD和TP mRNA与蛋白表达不受5-FU影响。结论:胃肠道肿瘤细胞内,DPD和TP表达在蛋白水平上受5-FU调控,而正常细胞不受影响。
BACKGROUND & AIM: Fluorouracil (5-FU) is the first choice and basic drug for gastrointestinal cancer chemotherapy. Its rate-limiting enzyme, dihydropyrimidine dehydrogenase (DPD) and catalase-thymidine phosphate The enzyme (TP) determines the concentration and effect of the drug in the tumor area and correlates with the chemosensitivity of 5-FU. The aim of this study was to investigate the role of 5-FU in regulating the expression of DPD and TP in gastrointestinal cancer cells. Methods: The gastric cancer cell line SGC7901, the human colorectal cancer cell line SW1116 and the human umbilical vein endothelial cell ECV-304 were selected and treated with different concentrations of 5-FU for different time, and then detected by RT-PCR, ELISA and immunohistochemistry DPD and TP mRNA and protein content, the effect of drugs on the expression of different metabolic enzymes in cells. Results: 5-FU showed different effects on different cells: the DPD protein levels of both SGC7901 and SW 1116 cells were up-regulated in a time-dependent manner, and TP protein expression was up-regulated in the two cell lines , High-dose down-regulation of dual effects, and with prolonged expression increased; 5-FU DPD and TP mRNA levels did not change significantly. The DPD and TP mRNA and protein expression of ECV-304 cell line were not affected by 5-FU. Conclusion: The expression of DPD and TP in gastrointestinal tumor cells is regulated by 5-FU at the protein level, while the normal cells are not affected.