腺病毒介导的胞嘧啶脱氨酶基因对小鼠肝癌的治疗

目的 探讨腺病毒介导的胞嘧啶脱氨酶基因对小鼠肝癌的基因治疗效果。方法 分离纯化ＡｄＣＤ，体外实验观察ＩＣ５０，旁观者效应及凋亡现象。在体内，ＡｄＣＤ瘤内注射并腹腔注射５ＦＣ，观察ＡｄＣＤ／５ＦＣ系统对肝瘤荷瘤小鼠的抗肿瘤效应。结果 当ＭＯＩ＝１００时，ＡｄＣＤ感染的ＭＭ４５Ｔ．Ｌｉ细胞对５ＦＣ敏感，ＩＣ５０〈５０μｍｏｌ／Ｌ。当ＡｄＣＤ感染的ＭＭ４５Ｔ．Ｌｉ细胞占１０％时，可有７２％细胞死亡，Ａｄ

Gene therapy for murine liver cancer by adenovirus-mediated cytosine deaminase gene

OBJECTIVE: To investigate anti-tumor effects of AdCD/5FC system on mice bearing MM45T.Li liver cancer. METHODS: IC(50), bystander effect and cell apoptosis were observed in vitro. After treatment of the tumor with AdCD in situ and injection of 5FC peritoneally into the mice, the anti-tumor effects were observed. RESULTS: When MOI=100, AdCD infected MM45T.Li was sensitive to 5FC, and the IC(50) was less than 50 micromol/L. When 10% MM45T.Li cells were infected with AdCD, 72% cells died after 5FC treatment, which showed significant bystander effect. Through TUNEL test and Hoechst 33258 staining, it was demonstrated that there was cell apoptosis after AdCD/5FC treatment of the MM45T.Li cell 21 day after treatment of the mice bearing tumor. The tumor volume was reduced significantly (F=20.33, P<0.05), and the median survival time was prolonged from 41-43 day to 49 day. CONCLUSION: AdCD/5FC system shows significant anti-tumor effects.