Repressing effects of double suicide genes system on human cholangiocarcinoma in vivo and in vitro / 中国普通外科杂志

ABSTRACT

Objective To investigate the repressing effects of cytosine deaminase(CD) and herpes simplex(virus) thymidine kinase(HSV-tk) double suicide genes coexpression system on human cholangiocarcinoma QBC939 cells and QBC939 cells transplantated tumor in nude mice.Methods CD and HSV-tk double suicide genes were transfered into QBC939 cells using liposomes.After G418 selection,the positive clones of QBC939/CD+tk cells were picked up and cultured.The expression of CD and HSV-tk genes was(confirmed) by RT-PCR.In vitro,the QBC939/CD+tk cells were treated with 5-Fc and/or GCV,and the cytoxicity efficacy was evaluated by microculture tetrajolium test(MTT) method.The QBC939/CD+tk cells were inoculated subcutaneously into nude mice,and when the tumors were palpable,5-Fc and GCV were(injected) intraperitoneally,and the volumes of transplantated tumors were measured before and after medication.Results Double suicide genes were stably expressed in QBC939/CD+tk cells.The repressing capability of combination of 5-Fc and GCV on QBC939/CD+tk cells was more effective than that of using either 5-Fc or GCV alone.The increase of cell-repressing was assaciated with increase the concentration of the prodrug.The repressing effect of combination of the 2 prodrugs on early period of transplantation tumor was obvious,even complete abolition of tumor was noted,and moreover a marked local bystander effect was observed.(Conclusions) In vitro and in vivo,the cell-repressing efficacy of double suicide gene system on cholongiocarcinoma cells and the tramsplanted tumor of nude mice was significant,and the bystander effect was obvious.