摘要
目的 探讨单纯疱疹病毒胸苷激酶 (HSV TK)基因联合羟基无环鸟苷 (GCV)对膀胱癌细胞的旁观杀伤作用及其机制。 方法 将转染HSV TK基因的膀胱癌细胞 (BIU 87 TK)分别与人膀胱癌细胞 (BIU 87、T 2 4)和鼠膀胱癌细胞 (T 739)混合培养。在GCV作用下 ,观测细胞的存活情况及BIU 87 TK条件培养液和细胞死亡裂解对共培养细胞的影响。 结果 当BIU 87 TK细胞占5 0 %时 ,共培养细胞对GCV的敏感性与 10 0 %BIU 87 TK细胞一致。表明每个表达HSV TK基因的细胞能杀死至少一个不含HSV TK基因的膀胱癌细胞。BIU 87 TK细胞的条件培养液对BIU 87亲本细胞的生长无影响。G 418诱导的细胞裂解对与其共培养的BIU 87 TK细胞无旁观毒性作用。 结论 HSV TK/GCV对膀胱癌细胞产生的“旁观者”效应是该系统特异性的毒性作用。“旁观者”效应不仅可在人膀胱癌不同细胞株之间产生 ,而且不局限于某一种属的膀胱癌细胞之间。
Objective To investigate the bystander tumoricidal effect mediated by HSV-TK/GCV system on the bladder cancer cells and the possible mechanisms of bystander effects. Methods HSV-TK gene-transduced BIU 87 cells (BIU 87-TK) were cocultured with the human bladder cancer cells (BIU 87,T 24)and a mouse bladder carcinoma cell line (T 739).In the presence of ganciclovir,the cell survival rate was monitoried.In addition the influence of the conditioned media from cultures of BIU 87-TK and G 418-induced cell lysis on cocultured cells was studied. Results When the proportion of BIU 87-TK cells is about 50%,the cocultures that contained 50% BIU 87-TK cells were as sensitive to GCV as cultures containing 100% BIU 87-TK cells.This indicated that one cell expressing HSV-TK gene was capable of me- diating death to at least one tumor cell carrying no HSV-TK genes.The conditioned media from cultures of BIU 87-TK cells in the presence of GCV exhibited no effects on survival of the BIU 87 parental cells.G 418-induced cell lysis did not mediate bystander cytocidal effect on the co-cultured BIU 87-TK cells. Conclusions The bystander effect among the bladder carcinoma lines in this study,which is not mediated by the cytotoxic effects of cell lysis or by a soluble factor(r) by culturing HSV-TK cells,is specific for cytotoxicity induced by HSV-TK/GCV system.In addition,the bystander effect can function between cells of diffe- rent human bladder tumors,and is not restricted to bladder cancer cell of a particular specie.
出处
《中华泌尿外科杂志》
CAS
CSCD
北大核心
2001年第5期284-287,共4页
Chinese Journal of Urology
基金
重庆市科技基金资助! (1997 5 3 )