单核细胞增强5′-脱氧氟尿苷抗结直肠癌细胞活性  

Monocyte enhances anticancer effect of 5'-deoxy-5-fluorouridine on colorectal carcinoma cells

作　　者：张继民[1] 刘明姬[2] 溝井贤幸 椎葉健一 佐々木嚴 松野正纪[3] 

机构地区：[1]广州医学院第二附属医院胃肠外科,510260 [2]中山大学黄埔医院麻醉科 [3]日本东北大学医学部第一外科

出　　处：《中华胃肠外科杂志》2003年第6期405-408,共4页Chinese Journal of Gastrointestinal Surgery

基　　金：教育部留学人员科研启动基金(教外司留[2002]247号)

摘　　要：目的 探讨巨噬细胞在结直肠癌化疗中的调控作用。方法 应用ELISA法分别检测结直肠癌细胞系LS174T、Clone A、Colo320、MIP101的胸苷磷酸化酶(dThdPase)蛋白含量。采用MTT分析,分别测定出氟尿嘧啶(5-FU)和5’-脱氧氟尿苷(5’-DFUR)对上述4种癌细胞的半数有效浓度(IC50)。然后把5’-DFUR加入培养基中同人血单核细胞一起培养24 h,其培养上清液2倍稀释后加入结直肠癌细胞中行MTT分析测定其IC50有无改变。同时测定单核细胞在不同浓度5’-DFUR中的存活率。结果 4种结直肠癌细胞仅LS174T检出0.5 U/mg的dThdPase蛋白,其它3种未检出。4种癌细胞对5-DFUR的IC50均明显高于5-FU(P<0.01)。同人血单核细胞一起培养后,5’-DFUR对4种癌细胞的IC50明显下降,仅相当于处理前的11.6％～34.3％(P<0.05),同时发现5’-DFUR对人血单核细胞无明显生长抑制作用。结论 被检结直肠癌细胞因缺乏dThdPase活性,不能在细胞内转化抗癌药物5’-DFUR为5-FU发挥细胞毒作用;同人血单核细胞一起培养后,5’-DFUR在单核细胞内dThdPase的催化下,可转化成5-FU并释放到培养基中发挥抗癌作用。Objective To investigate the enhanced antitumor effect of thymidine phosphorylase (dThdPase) expressed in human monocyte by converting 5'-deoxy-5-fluorouridine(5'-DFUR) to 5-flurouracil (5-Fu) on 4 colorectal cancer cell lines. Methods dThdPase contents were examined in 4 colorectal cancer cell lines, LS174T, Clone A, Colo320 and MIP101 by ELISA method. MTT assay was used to examine drug sensitivity of these 4 cancer lines to 5'-DFUR and 5-Fu, and the mean IC50 was calculated respectively. Monocytes were isolated from human blood and incubated in the 5'-DFUR-containing media for 24h. 4 cancer cell lines were added to the diluted supernatants and incubated for 96h, then drug sensitivity was also examined by MTT assay. The survival rates of monocytes in different dilutions of 5'-DFUR were examined. Results The dThdPase level was 0. 5 U/mg in LS174T cells, but not detected in other 3 colorectal cancer cells. All colorectal cancer cells examined were resistant to 5'-DFUR, and the mean IC50 values were 15 to 94 times higher than those of 5-Fu. After incubation with monocytes, the antitumor effect of 5'-DFUR was enhanced, and the mean IC50 values of 5'-DFUR decreased to only 11.6% - 34. 3% as compared with those of untreated values. No significant difference was found in the survival rate of monocytes cultured in different dilution of 5'-DFUR. Conclusions 5'-DFUR can not be converted to 5-Fu in colorectal cancer cells examined because of no dThdPase expression in these cells. After incubation with human monocytes, the antitumor effect of 5'-DFUR can be enhanced due to the conversion to 5-Fu by dThdPase in monocytes.

关 键 词：单核细胞 细胞活性 结肠癌 5′-脱氧氟尿苷 5’-DFUR 直肠癌 

分 类 号：R735.3[医药卫生—肿瘤]