Antitumor activity of 5' -deoxy-fluorouridine on colon cancer experimental model in BALB/C mice / 国际外科学杂志

ABSTRACT

ObjectiveTo evaluate the anticancer activity of 5'-dexoxy-fluorouridine on colon cancer experimental models in BALB/C mice,compared with 5'-fluorouracil,an anticancer agent widely used in clinic,meanwhile,examined the conversion of 5'-Dexoxy-fluorouridine to 5' -fluorouracil in cancer tissues and serum of mouse models.MethodsThe xenografts of mouse colon cancer cell line CT 26 were transplantated to cecum in 60 male BALB/C mice.Three days lated,these mice were divided into 3 groups and intro- peritoneally injected( 1 ) 5' - dexoxy- fluorouridine 0.1 mg/g,(2) 5' - Fluorouracil 0.02 mg/g,(3)0.9％ sodium chloride 0.4 mL (as a control),respectively.Two and three weeks later,6 mice were sacririced in every group respectively to measure the weight of tumors and bodies,to examine the Hb,RBC,WBC,PLT,AST,ALT,UREA,and CREA in blood.The rest 8 mice in each group were fed generally,and the survival time from operation to natural death was recorded.In addition,14 mice with xenografts of CT 26 about 2 weeks,were divided into 2 groups averagely,5' -dexoxy-fluorouridine 0.1 mg/g and 5' -fluorouracil 0.02 mg/g were intro-peritoneally injected respectively.Fifteen min later,the converted 5' -fluorouracil was detected from the blood and tumor tissues in sacrificed mice.ResultsThe lest tumor average weight was found in the mice injected 5 '-dexoxy-fluorouridine,being (0.07 ± 0.12) g and (0.24g ±0.29) g for the mice sacrificed at 2 and 3 weeks later,respectively.The average survival time for rest mice was ( 32.6 ± 8.9) d.The average tumor weight in 5' - fluorouracil group was (0.74 ± 0.43 ) g and ( 1.13 ±0.75) g at 2 and 3 weeks later,and the average survival time for the rest was (22.8 ±5.9)d,respectively.The average tumor weight in the control group was (0.70 ±0.47) g and ( 1.93 ±0.83) g at 2 and 3 weeks,and the average survival time for the rest was ( 17.5 ± 2.8 ) d.Either the average tumor weight or average survival time in the mice of 5 ' -dexoxy-fluorouridine group was significantly differen from either 5' -fluorouracil group or control (P ＜ 0.05 ).However,there was no significant difference for the numbers of WBC,PLC,Hb,and some function examination of liver and kidney among 3 group mice,besides the loss of weights in 5'-fluorouracil group mice after operation and medicine therapy which was significantly obvious than that in 5' -deoxy-fluorouridine and control groups ( P ＜ 0.05 ).In addition,( 54.71 ± 12.82) μg/g 5' -fluorouracil was detected in xenografts of mice injected 5' -dexoxy-fluorouridine 15 min later,which was the 6.20 folds of 5' -fluorouracil detected in serum from sthe ame group,P ＜0.05.However,( 133.35 ±20.69) μg/m 5'-fluorouracil were detected in serum of mice after 5' -fluorouracil were injected 15 min later,which was the 1.55 folds of 5' -fluorouracil detected in the xenografts from same group ( P ＜ 0.05 ).ConclusionsIn colon cancer tissues of mouse experimental models,5' - dexoxy- fluorouridine could be converted effectively to 5'-fluorouracil,an obvious high concentration being detected in serum of mice than in cancer tissues.The anticancer effect of 5'-dexoxy-fluorouridine on mouse colon cancer models was more effective than 5'-fluorouracil,resulting in a longer survival duration,less side effect and no significant injury on liver and kidney functions.However,the mechanism of 5' -dexoxy-fluorouridine converted to 5' -fluorouracil in cancer tissue is needed further investigation.