HSV-TK/GCV系统对前列腺癌细胞的杀伤作用和旁观者效应

The killing and bystander effect of HSV TK/GCV approach on prostate cancer cells

目的 :研究胸苷激酶 (TK)自杀基因疗法对人前列腺癌细胞的杀伤作用和旁观者效应 ,探讨其治疗前列腺癌的可行性。方法 :采用形态学观察、活细胞拒染法及MTT法检测单纯疱疹病毒胸苷激酶 (HSV TK) /羟基无环鸟苷 (GCV)系统对前列腺癌细胞的杀伤作用及旁观者效应。结果 :GCV对转染TK基因前列腺癌细胞的杀伤作用呈剂量及时间依赖关系 (P <0 .0 5～ 0 .0 1) ;但其旁观者效应较弱 ,TK基因阳性细胞比例约为 10 %的混合细胞 ,经 10 μmol/L和 10 0 μmol/L的GCV处理 72h后 ,仅有16.15 %± 1.64 %和 2 3 .46%± 3 .2 1%的细胞被杀灭。结论 :HSV TK/GCV系统对前列腺癌有杀伤作用 ,但由于其旁观者效应不够强大 。

Purpose:To investigate the killing and bystander effect of TK suicide gene therapy on human prostate cancer (PCa) cells and discuss the feasibility of the approach for PCa therapy. Methods:The killing and bystander effect mediated by HSV TK/GCV system were evaluated by morphological examination, trypan blue exclusion and MTT assay.Results:GCV could play a cytotoxicitic role on TK gene transduced PCa cells with a time and dose dependent manner (P< 0.05 ～ 0.01 ), but the extents of the bystander effect were not of significance. Posterior to 72 hour treatment of 10 μmol/L and 100μmol/L GCV on mixtures of 90% wild type with 10% HSV TK gene modified PC 3 m prostate adenocarcinoma cells, 16.15 %± 1.64 % and 23.46 %± 3.21 % cells were killed respectively. Conclusions:Simplex HSV TK/GCV system can acts as a candidate treatment for PCa therapy, while it was not expected to achieve a magnificent outcome because of its poor-magnitude bystander effect.