CD/5-FC自杀基因体系在正常免疫力动物体内的抑瘤及旁观者效应

Tumor inhibition and bystander effect of CD/5-FC suicide gene system in normal mice

目的:观察阳离子脂质体介导的CD/5-FC自杀基因体系协同γ-IFN在正常免疫力小型动物体内对肿瘤的抑制效应及远端旁观者效应.方法:采用阳离子脂质体介导CD基因质粒瞬时转染小鼠肝癌H22及空质粒转染的H22细胞,分别接种于KM鼠双侧前腋下皮下;向小鼠体内注射5-FC及γ-IFN,观察在γ-IFN协同作用下对转染CD基因瘤体的抑制作用和远距离空质粒转染瘤体的抑制即远端旁观者效应.结果:5-FC对转染CD基因侧瘤体抑制明显,抑制率为79.39%;在γ-IFN的协同下CD/5-FC的抑瘤作用得到了增强,抑制率为93.47%,与无γ-IFN协同作用相比,对癌细胞抑制率明显增强(t=3.49,P=0.0036);存在远端旁观者效应,远端未转染瘤体的抑制率为54.42%;在γ-IFN的协同下远端旁观者效应得到显著增强,抑制率达到88.43%,同无γ-IFN相比有差异有显著性(t=2.86,P=0.0212).结论:体内CD/5-FC自杀基因体系联合γ-IFN对肝癌细胞有更好的抑制效应,对肝癌的治疗有很好的应用前景.

AIM： To investigate the anticancer and distant bystander effect of CD/5-FC suicide gene system combined with γ-IFN in normal mice. METHODS： H22 cells instantly transfected with cytosine deaminase （CD） gene plasmid （lipo-CD） or empty plasmid, mediated by cation liposome, were subcutaneously inoculated into the left or right axilla of Kunming mice, respectively. Then the mice were injected with 5-FC and γ-interferon （γ-IFN） once per day, and the anticancer effect and distant bystander effects were compared when γ-IFN was used or not. RESULTS： 5-FC obviously inhibited the growth of tumors transfected with lipo-CD, and the inhibitory efficiency was 79.39%. When in com- bination with γ-IFN, the inhibitory efficiency （93.47%） was strengthened significantly （t = 3.49, P = 0.0036）. There was a notable bystander effect in CD/5-FC suicide gene system in vivo, and the suppressive rate was 54.42% for the distant tumor cells without transfection. When in combination with 7-IFN, the inhibition rate （88.43%） was strengthened greatly （t = 2.86, P = 0.0212）. CONCLUSION： CD/5-FC suicide system combined with 7-IFN has more significant anticancer effects and may be used as a promising method in the treatment of liver cancer.