前药5-FC联合胃泌素拮抗剂CI-988对转CD基因大肠癌SW480细胞的杀伤作用

Gastrin receptor antagonist CI-988 enhances killing effect of prodrug 5-FC on human colorectal carcinoma cell lines SW480 transfected cytosine deaminase gene

目的:探讨联合应用前药5-氟胞嘧啶(5-fluorocytosine,5-FC)和胃泌素拮抗剂CI-988对转组织特异性胞嘧啶脱氨基酶(cytosine deaminase,CD)基因的大肠癌SW480细胞生长的影响。方法:将转CD基因大肠癌SW480细胞接种至4块24孔细胞培养板中,依次分为实验组1、2、3及对照组,分别以含有前药5-FC、胃泌素拮抗剂CI-988、5-FC联合CI-988及正常培养液进行培养。每天胰酶消化法计数各组4孔,共6d,绘制细胞生长曲线并计算生长抑制率。按上述分组方法另接种培养4组细胞,于培养72h行MTT法检测490nm处吸光度A值,计算细胞杀伤率。结果:应用5-FC联合CI-988处理的转CD基因大肠癌SW480细胞在6d后生长抑制率达97;于培养72h时,实验组1、3细胞杀伤率较对照组有显著性差异(P<0.01);实验组2与对照组无显著性差异(P>0.05);实验组3较实验组1、2有显著性差异(P<0.01)。结论:CD/5-FC系统和胃泌素拮抗剂CI-988对转基因大肠癌SW480细胞具有杀伤或抑制作用,联合应用胃泌素拮抗剂可以提高CD/5-FC自杀基因系统对大肠癌细胞的杀伤效应。

Objective ：To investigate the killing effect of prodrug 5 -fluorocytosine （f-FC） with gastrin receptor antagonist CI- 988 on human colorectal cancer cell lines SW480 transfected cytosine deaminase（CD）. Methods： The human colorectal carcinoma cell lines SW480 transfected CD gene were cultured and divided into the group 1,2, 3 and the control group ： the group 1 and group 2 were respectively treated with prodrug 5 - FC and CI - 988 singular- ly, the group 3 was administrated the both agents simultaneously. Everyday cells of 4 apertures of every group were digested by trypsin and counted for 6 days, and drawing the cellular growth curve. MTT was used to detect the cellular survival rates at 72h. Results ：The inhibition rate of cell growth was 97% on 6d when combine 5 - FC and CI -988. The cellular survival rates of the group 1,3 were significantly lower than that of the control group（ P 〈 0.01 ） ,whereas no significant difference showed between the cellular survival rate of the group 2 and of control group（P 〉 0.05 ）. The cellular survival rate of the group 3 was significantly lower than that of the control group 1,2 （ P 〈 0.0I ）. Conclu- sion ： CD/5 - FC system and gastrin antagonist CI - 988 have the killing or inhibitive effects on human colorectal car- cinoma cell lines SW480 transfected CD gene. Significantly synergetic effects were observed when combined gastfin antagonist and CD/5 -FC system.