Antitumor activity of mutant bacterial cytosine deaminase gene for colon cancer

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:dongjun1964
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AIM:To evaluate bacterial cytosine deaminase(bCD) mutant D314A and 5-fluorocytosine(5-FC) for treatment of colon cancer in a mouse model.METHODS:Recombinant lentivirus vectors that contained wild-type bCD gene(bCDwt),and bCD mutant D314A gene(bCD-D314A) with green fluorescence protein gene were constructed and used to infect human colon carcinoma LoVo cells,to generate stable transfected cells,LoVo/null,LoVo/bCDwt or LoVo/bCDD314A.These were injected subcutaneously into Balb/c nude mice to establish xenograft models.Two weeks post-LoVo cell inoculation,PBS or 5-FC(500 mg/kg) was administered by intraperitoneal(i.p.) injection once daily for 14 d.On the day after LoVo cell injection,mice were monitored daily for tumor volume and survival.RESULTS:Sequence analyses confirmed the construction of recombinant lentiviral plasmids that contained bCDwt or bCD-D314A.The lentiviral vector had high ef-ficacy for gene delivery,and RT-PCR showed that bCDwt or bCD-D314A gene was transferred to LoVo cells.Among these treatment groups,gene delivery or 5-FC administration alone had no effect on tumor growth.However,bCDwt/5-FC or bCD-D314A/5-FC treatment inhibited tumor growth and prolonged survival of mice significantly(P < 0.05).Importantly,the tumor volume in the bCD-D314A/5-FC-treated group was lower than that in the bCDwt/5-FC group(P < 0.05),and bCDD314A plus 5-FC significantly prolonged survival of mice in comparison with bCDwt plus 5-FC(P < 0.05).CONCLUSION:The bCD mutant D314A enhanced significantly antitumor activity in human colon cancer xenograft models,which provides a promising approach for human colon carcinoma therapy. AIM: To evaluate bacterial cytosine deaminase (bCD) mutant D314A and 5-fluorocytosine (5-FC) for treatment of colon cancer in a mouse model. METHODS: Recombinant lentivirus vectors that contained wild- type bCD gene The D314A gene (bCD-D314A) with green fluorescence protein gene were constructed and used to infect human colon carcinoma LoVo cells, to generate stable transfected cells, LoVo / null, LoVo / bCDwt or LoVo / bCDD314A.These were injected subcutaneously into Balb / c nude mice to establish xenograft models. Two weeks post-LoVo cell inoculation, PBS or 5-FC (500 mg / kg) was administered by intraperitoneal (ip) injection once daily for 14 days. monitored daily for tumor volume and survival. Results: sequences analyzed by the construction of recombinant lentiviral plasmids that contained bCDwt or bCD-D314A.The lentiviral vector had high ef-ficacy for gene delivery, and RT-PCR showed that bCDwt or bCD-D314A gene was transferred to LoVo c These treatment groups, gene delivery or 5-FC administration alone had no effect on tumor growth. However, bCDwt / 5- FC or bCD-D314A / 5-FC treatment inhibited tumor growth and prolonged survival of mice significantly (P < 0.05) .Importantly, the tumor volume in the bCD-D314A / 5-FC-treated group was lower than that in the bCDwt / 5- FC group (P <0.05), and bCDD314A plus 5-FC significantly prolonged survival of mice in comparison with bCDwt plus 5-FC (P <0.05). CONCLUSION: The bCD mutant D314A enhanced significantly antitumor activity in human colon cancer xenograft models, which provides a promising approach for human colon carcinoma therapy.
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