xperimental Study on Adenovirus-Mediated Suicide Gene Therapy for Human Hepatucellular Carcinoma Using Escherichia Coli Cytosine Deaminase / 中国肿瘤生物治疗杂志

ABSTRACT

To evaluate whether in vitro and in vivo transfer of E. Coli cytosine deaminase gene will confer sensitivity of a solid tumor to prodrug 5-fluorocytosine(5FC), we used an adenovirus vector(AdexCMV. CD) carrying the cytosine deaminase gene driven by the CMV promoter, infected SMMC-7721 or HepG2 cells hepatocellular carcinoma cells in vitro, and found AdexCMV. CD vector could effectively suppressed the growth of SMMC-7721 and HepG2 cells. When the two cells were infected with AdexAFP. CD vector in which the CD gene was driven by the AFP gene 5'-flanking region, only HepG2 cells were conferred sensitivity to 5FC. (Infection with AdexCMV.CD, when as few as 20% of cells transfected the CD gene, SMMC-7721 cells were associated with a bystander effect when combined with 5FC in cell mixing studies.) Consistent with these in vitro observations, AdexCMV. CD was directly injected into established subcutaneous SMMC-7721 tumors in nude mice receiving 5FC,there was a 60% reduction in tumor size at day 8, 70% reduction at day 24. Our results suggested that adenovirus-mediated tumor-specific gene transfer of CD gene and concomitant administration of 5 FC may have potential as a strategy for local control of tumor growth.