Objective:To investigate the target effect of cytosine deaminase genetherapy combined thermochemotherapy on liver metastasis of colon cancer in nude mice.
Methods:Plasmid G1CEACDNa were transferred into the human colon cancer LoVo cells by liposomes method. The models of liver metastasis of colon cancer were established by injected LoVo-CEACD into peritonum in 45 BALB/C nude mice, then which were randomly divided into three groups: The control (C) group; the prodrug therapy (PDT) group and the prodrug thermochemotherapy (PDTCT group) and 42 ℃ sodium chloride，38 ℃ 5-FC and 42 ℃ 5-FC were injected into the abdominal cavity ［500 mg/（kg·d）,for 21 d］, respectively. After natural death of all mice, their life span, rate of liver metastasis and number of liver metastasis nodules were surveyed and compared among the three groups. The levels of the expression of target gene were detected by RT-PCR in carcinoma tissue, normal liver, stomach，lung，pancreas，small intestine and large intestine tissues. Pathological features were observed. Apoptotic index (AI) of tumor cells were analyzed in every group respectively.
Results:The CD gene was detected in the tumor tissues，but not in tissues of normal liver, stomach，lung，pancreas，small intestine and large intestine. In C,PDT and PDTCT group, the life span was （25.80±3.65）,（34.27±4.08） and （41.87±3.91）d respectively; the rate of liver metastasis was 100.0%(15/15),40.0%(6/15) and 13.3%(2/15), respectively; the number of liver metastasis nodules was（2.93±1.16）,（0.80±1.01） and （0.20±0.56）, respectively; and AI of tumor cells was 4.59%,9.87%,17.4%, respectively. The life span of PDT and PDTCT guoup was significantly longer than that of group (P＜0.05);the rate of liver matastasis and AI of tumor cells were obvious differences between the 3 groups.
Conclusions:The CEA tissue-specific CD/5-FC system has an obvious target suppression on liver metastasis of colon cancer cell LoVo in nude mice.