Antitumor Activity Of Mutant Bacterial Cytosine Deaminase Gene For Colon Cancer

AIM: To evaluate bacterial cytosine deaminase (bCD) mutant D314A and5-fluorocytosine (5-FC) for treatment of colon cancer in a mouse model.MATERIALS AND METHODS: Recombinant lentivirus vectors thatcontained wild-type bCD gene (bCDwt), and bCD mutant D314A gene (bCD-D314A)with green fluorescence protein gene were constructed and used to infect humancolon carcinoma LoVo cells, to generate stable transfected cells, LoVo/null,LoVo/bCDwt or LoVo/bCD-D314A. These were injected subcutaneously into Balb/cnude mice to establish xenograft models. Two weeks post-LoVo cell inoculation,PBS or5-FC (500mg/kg) was administered by intraperitoneal (i.p.) injection oncedaily for14d. On the day after LoVo cell injection, mice were monitored daily fortumor volume and survival.RESULTS: Sequence analyses confirmed the construction of recombinantlentiviral plasmids that contained bCDwt or bCD-D314A. The lentiviral vector hadhigh efficacy for gene delivery, and RT-PCR showed that bCDwt or bCD-D314Agene was transferred to LoVo cells. Among these treatment groups, gene delivery or5-FC administration alone had no effect on tumor growth. However, bCDwt/5-FC orbCD-D314A/5-FC treatment inhibited tumor growth and prolonged survival of micesignificantly(P<0.05).Importantly, the tumor volume in the bCD-D314A/5-FC-treatedgroup was lower than that in the bCDwt/5-FC group (P <0.05), and bCD-D314A plus5-FC significantly prolonged survival of mice in comparison with bCDwt plus5-FC (P <0.05).CONCLUSION: The bCD mutant D314A enhanced significantly antitumoractivity in human colon cancer xenograft models, which provides a promisingapproach for human colon carcinoma therapy.