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Therapeutic Effect of YCD Suicide Gene-Modified Murine P388 Leukemia in vivo
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Abstract:
Objective: To explore therapeutic effect of a novel yeast cytosine deaminase (YCD) suicide gene in vivo on P388/DBA murine leukemia model. Methods: P388-YCD-eGFP clone was selected after retrovirus transduction by limiting dilution, P388-eGFP and wild type (wt) P388 were used as control. (1) Tumorigenesis study: DBA mice were inoculated with P388-YCD-eGFP, P388-eGFP or wt P388, 5×10 6/each i.p. (n=5). (2) 5-FC therapy study: After inoculation with P388-YCD-eGFP, P388-eGFP and wt P388 respectively (n=5)，each mouse was given 5-FC with a dose of 5 μmol/d×2 w. (3) 5-FC killing effect study: 2 groups (n=5) of mice inoculated with P388-YCD-eGFP were treated with 5-FC×2 d or PBS. Results: Mice in YCD, eGFP and wtP388 group developed leukemia and survived for (8±1.0) d, (7.6±0.89) d and (7.8±1.64) d (P>0.05), respectively. After 5-FC-2w-treatment, mice in YCD group survived (17.8±1.89) d (P<0.05) vs (7.8±1.10) d (eGFP) and (7.7±1.15) d (wtP388) group, respectively. Mice of YCD group with 5-FC-2 d-treatment survived for (13.3±2.36) d，while PBS group (8.0±1.15) d. Flow cytometry and pathological examinations suggested mice of in YCD group died of leukemia relapse. Conclusion: YCD/5-FC is an efficient suicide gene system in vivo.
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