In Vitro and In Vivo Tissue Specific Cytotoxicity of Gastric Cancer Cells Resulting from CD:UPRT/5-FC Gene Therapy System Driven by hTERT Promoter

摘要

Gastric carcinoma is one of the most frequent cancers worldwide. The currently available clinical treatments rarely cure the disease. Gene therapies have received much attention. Suicide gene of CD/5-FC is considered to be a promising approach. However, the low efficiency of conversion of 5-FU to its toxic metabolites might be a major reason for the failure of CD/5-FC system, and therefore our combination of CD with UPRT is expected to overcome this problem. The hTERT (human telomerase catalytic subunit) gene promoter was fused with the CD:UPRT (cytosine deaminase-uracil phosphoribosyhransferase) gene. This fused gene was delivered into SGC7901. After adding prodrug 5-FC, the therapeutic effect was evaluated in vitro and in vivo. Our study showed that the hTERT promoter could effectively drive the target gene to express only in hTERT-positive gastric cancer cells. The CD:UPRT/5-FC gene therapy system driven by hTERT promoter resulted in significant cytotoxicity and "bystander effect" in vitro. Moreover, this combined gene therapy significantly caused delay of tumor growth in xenografted human gastric carcinoma in vivo. Our study demonstrated that the CD:UPRT/5-FC gene therapy system driven by hTERT promoter could be a promising approach for hTERT-positive tumor gene therapy.