Anticancer Efficacy Of Combining Cytosine Deaminase/5-fluorocytosine Gene Therapy And Radiotherapy To Cervical Carcinoma

Objective: This study is aimed to observe the effect of combining cytosinedeaminase(CD)/5-fluorocytosine(5-FC) gene therapy with radiotherapy on cervical carcinoma in nude mouse and to observe if there is a synergistic effect between the two therapies.Methods: Hela cells of 2× 10~6 per mouse were injected in the right hindlegs of the 24 female nude mice who were 6-8 weeks old. When the tumors grew to 4-7mm in diameter, the mice were divided into 4 groups randomly: (1)control group; (2)CD/5-FC gene therapy group; (3)CD/5-FC gene therapy plus radiotherapy group; ?radiotherapy group. In the control group, every mouse was injected with Natural Saline(NS) 1ml in the abdominal cavity for consecutively 21 days; 50 μ 1 NS was injected into the tumors every 3 days for 7 times. Each mouse in the CD/5-FC gene therapy group was injected with 5-FC 500mg/kg/1ml in the abdominal cavity for consecutively 21 days;1 X 10 pfu/50 U 1 replication-defective recombinant adenovirus vector containing CMV promoter and Escherichia coli cytosine deaminase gene (AdCMVCD) was injected into the tumors every 3 days for 7 times. In the CD/5-FC gene therapy plus radiotherapy group, every mouse was injected with 5-FC 500mg/kg/lml in the abdominal cavity for consecutively 21 days; 1 X 108pfu/50 ii 1 AdCMVCD was injected into the tumors every 3 days for 7 times; And 60Co radiation was administrated locally at 5 Gy each time, every 6 days, for 2 times, with a total of 10 Gy. To each mouse in the radiotherapy group, 60Co radiation was administrated locally at 5 Gy each time, every 6 days, for 2 times, with a total of 10 Gy.The volumes and inhibiting rates of the tumors were calculated.Results:l.In CD/5-FC gene therapy group(728.16±200.88mm3), CD/5-FCgene therapy plus radiotherapy group(356.80+113.31 mm3)> radiotherapy group(738.91 ± 419.44 mm3) ,there were smaller volumes of tumors compared with that in the control group(l 168.06±380.4 mm3),the difference had a statistical significance(P<0.05); CD/5-FC gene therapy plus radiotherapy group had a significantly smaller tumor volume compared with that in the CD/5-FC gene therapy group and radiotherapy group (PO.05); the difference of tumor's volumes between CD/5-FC gene therapy group and radiotherapy group had no statistical significance(P>0.05). 2.The tumor-inhibiting rate of the radiotherapy group was 36.74%, the CD/5-FC gene therapy group was 37.66%, and the CD/5-FC gene therapy plus radiotherapy group was 69.45%, significantly higher than that of the radiotherapy group and the CD/5-FC gene therapy group(P<0.05). 3. There was a synergistic effect between CD/5-FC gene therapy and radiotherapy.Conclusion: The results showed that there was a synergistic effect betweenCD/5-FC gene therapy and radiotherapy. CD/5-FC gene therapy combined with radiotherapy may be a good supplementary method for cancer synthetic treatment.