慢病毒介导Gag-caspase-8对小鼠乳腺癌细胞移植瘤的抑制作用

Inhibitory effect of lentivirus-mediated Gag-caspase-8 on transplanted breast cancer in mice

目的:探讨慢病毒介导Gag-caspase-8对小鼠乳腺癌4T1细胞BALB/C移植瘤的抑制效果。方法:PEI转染法将Gag-caspase-8转入293T细胞包装,并收集病毒颗粒。BALB/C小鼠建立4T1乳腺癌移植瘤模型,按照数字表法随机分为对照组(注射等量PBS)、Gag-caspase-8治疗组(注射1×10^6/mL Gag-caspase-8)和Gag组(注射1×10^6/mL Gag)。在种植细胞第10天开始经瘤内注射Gag-caspase-8进行抑瘤实验,每只0.1 mL,每3 d给药1次,共计3次,观察小鼠移植瘤的生长情况;抑瘤实验第12天处死小鼠,采用免疫荧光法检测移植瘤组织caspase-8蛋白表达。结果:抑瘤实验12 d时,对照组、Gag组移植瘤体积明显高于Gag-caspase-8组,Gag-caspase-8组抑瘤率明显高于对照组,差异有统计学意义。Gag-caspase-8组Caspase-8蛋白表达高于对照组和Gag组,Gagcaspase-8组肺部转移结节数明显少于对照组,差异有统计学意义。结论:Gag-caspase-8慢病毒颗粒对小鼠乳腺癌荷瘤生长及肺转移有抑制作用。

Objective:To investigate the inhibitory effect of lentivirus-mediated Gag-caspase-8 on transplantion tumor mice with breast cancer.Methods:PEI method was used to transfect Gag-caspase-8 into 293T cells and virus particles were collected.BALB/C models of 4T1 breast cancer were established,and the tumor cells were successfully modeled after 10 d.According to the digital table method,Mice were randomly divided into control group(equal dose PBS),Gag-caspase-8 group(1×10^6/mL Gag-caspase-8)and Gag group(1×10^6/mL Gag).At the beginning of 10 d,the tumor cells were injected with Gag-caspase-8 to inhibit the tumor(0.1 mL,1 time every 3 days,for 3 times).The growth of transplanted tumor in mice was observed,and the mice were killed after the anti-tumor experiment on 12 d.The expression of caspase-8 protein in the transplanted tumor tissue was detected by immunofluorescence.Results:On 12 d after the tumor suppression experiment,the tumor size in Gag group and control group was significantly higher than that of Gag-caspase-8 group.The inhibition rate of Gag-caspase-8 group was significantly higher than that of the control group and empty vector group.The expression of caspase-8 protein in the Gag-caspase-8 group was significantly higher than that of the control group and Gag group.The number of pulmonary metastatic nodules of the LV-Gag-caspase-8 group was significantly decreased compared with that of the PBS control group.Conclusion:Gag-caspase-8 lentivirus particles can inhibit the growth of tumor bearing tumor and lung metastasis of breast cancer in mice.