摘要
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-干扰素活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基因瞬时转染小鼠肝癌H22及未转染的H22细胞,分别接种于昆明小鼠双侧前腋下皮下;向小鼠体内注射5-FC及γ-干扰素,观察在γ-干扰素协同作用下5-FC对转染瘤体的抑制作用和远处无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%(P<0.05);在γ-干扰素的协同下CD/5-FC的抑瘤作用得到了增强,抑制率为93.47%,与无γ-干扰素协同相比,对癌细胞抑制作用明显增强(P<0.05);存在远端旁观者效应,远端未转染瘤体的抑制率为54.42%(P<0.05);在γ-干扰素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-干扰素相比有差异有显著性(P<0.05)。结论体内CD/5-FC自杀基因体系联合γ-干扰素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。
Objective To study the antitumor and distant bystander effects of cationic liposome-mediated cytosine deaminase （CD）/5-fluorocytosine （5-FC） suicide gene system combined with interferon-γ, （IFN-γ） in vivo. Methods Murine hepatoma 22 （H22） cells transfected by CD gene were inoculated subcutaneous in Kunming mice in the left axillary region, and the H22 cells without CD gene transfection were inoculated in the right axillary region. The mice were randomly divided into 4 groups and treated with normal saline, 5-FC, IFN-γ and 5-FC＋ IFN-γ, on a daily basis. The tumor inhibition and distant bystander effects were observed in the mice. Results Exposure ofCD gene-transfected tumor to 5-Fc resulted in obvious tumor growth inhibition with an inhibition rate of 78.38%, which was significantly increased to 93.21% （P〈0.01） with 5-Fc ＋IFN-γ, treatment. A notable distant bystander effect in the CD/5-FC suicide gene system was observed in vivo, with a tumor inhibition rate of was 54.42%; when combined with IFN-γ the inhibition rate increased significantly to 87.57% （P〈0.05）. Conclusion When combined with IFN-γ CD/5-FC suicide system has stronger anti-tumor and distant bystander effects. CD/5-FC suicide gene system combined with IFN-γ, may provide a potential therapy for malignant tumors.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2008年第9期1621-1625,共5页
Journal of Southern Medical University
基金
福建省厦门市卫生局基金(wsk0509)
