Increased cytotoxicity and bystander effect of 5-fluorouracil and 5-deoxy-5-fluorouridine in human colorectal cancer cells transfected with thymidine phosphorylase.
Increased cytotoxicity and bystander effect of 5-fluorouracil and 5-deoxy-5-fluorouridine in human colorectal cancer cells transfected with thymidine phosphorylase.
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DOI：
10.1038/sj.bjc.6690589
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发表时间：
1999-08
影响因子：
8.8
通讯作者：
Cano, JP
中科院分区：
文献类型：
--
作者：
Evrard, A;Cuq, P;Ciccolini, J;Vian, L;Cano, JP
5-氟尿嘧啶（5-FU）及其前体5′-脱氧-5-氟尿嘧啶核苷（5′-DFUR）是由胸苷磷酸化酶（TP）激活的抗癌药物。将人TP cDNA转染到癌细胞中以使其对这些嘧啶抗代谢物敏感可能是人类癌症基因治疗研究的一种重要方法。本研究将含有人TP cDNA的表达载体（pcTP 5）转染人结肠癌细胞LS 174 T。随机选择8个稳定的转染子并进行分析。5-FU和5′-DFUR对TP转染细胞的细胞毒作用高于野生型细胞。5-FU和5′-DFUR的IC 50最大降低分别为80倍和40倍。TP转染细胞对这些嘧啶类药物敏感性的增加与TP活性和TP表达的增加显著相关。转染的克隆LS 174 T-c2而非野生型细胞显示由[3 H]5-FU形成[3 H]FdUMP。此外，LS 174 T-c2克隆增强了5′-DFUR对共培养的亲本细胞的细胞毒性作用，也增强了5-FU对共培养的亲本细胞的细胞毒性作用。对于这两种抗癌剂，这种旁观者效应不需要细胞-细胞接触。这些结果表明，5-FU或5′-DFUR可以与TP自杀载体一起用于癌症基因治疗。© 1999癌症研究运动
5-Fluorouracil (5-FU) and 5′-deoxy-5-fluorouridine (5′-DFUR), a prodrug of 5-FU, are anticancer agents activated by thymidine phosphorylase (TP). Transfecting the human TP cDNA into cancer cells in order to sensitize them to these pyrimidine antimetabolites may be an important approach in human cancer gene therapy research. In this study, an expression vector containing the human TP cDNA (pcTP5) was transfected into LS174T human colon carcinoma cells. Eight stable transfectants were randomly selected and analysed. The cytotoxic effects of 5-FU and 5′-DFUR were higher in TP-transfected cells as compared to wild-type cells. The maximal decreases in the IC50 were 80-fold for 5-FU and 40-fold for 5′-DFUR. The increase in sensitivity to these pyrimidines of TP-transfected cells significantly correlated with the increase in both TP activity and TP expression. Transfected clone LS174T-c2 but not wild-type cells exhibited formation of [3H]FdUMP from [3H]5-FU. In addition the LS174T-c2 clone enhanced the cytotoxic effect of 5′-DFUR, but also that of 5-FU, towards co-cultured parental cells. For both anti-cancer agents, this bystander effect did not require cell–cell contact. These results show that both 5-FU or 5′-DFUR could be used together with a TP-suicide vector in cancer gene therapy. © 1999 Cancer Research Campaign
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影响因子：
10.3
作者：
MOOLTEN, FL;WELLS, JM
通讯作者：
WELLS, JM
影响因子：
4.2
作者：
Denning, C;Pitts, JD
通讯作者：
Pitts, JD
DOI：
10.1016/0005-2787(81)90174-x
发表时间：
1981-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
DESGRANGES, C;RAZAKA, G;BRICAUD, H
通讯作者：
BRICAUD, H
影响因子：
2.9
作者：
MOGHADDAM, A;BICKNELL, R
通讯作者：
BICKNELL, R
影响因子：
6.1
作者：
Evrard, A;Vian, L;Cano, JP
通讯作者：
Cano, JP