Targeted killing effects of double CD and TK suicide genes controlled by survivin promoter on gastric cancer cell

摘要

Suicide genes such as cytosine deaminase (CD) and herpes simplex virus thymidine kinase (TK) encode products that convert nontoxic substances (prodrugs) into toxic metabolites. Studies in recent years indicated that survivin(sur) expression was associated with the biological behaviors of gastric carcinoma. In the present study, targeted killing effects of double CD and TK suicide genes controlled by survivin promoter on gastric cancer cell were investigated, the recombinant pSCT vector containing CD and TK genes driven by sur promoter was constructed and transfected into SGC-7901 cells. After adding the CCV and 5-FC, the effects of double suicide genes on cell growth, cell cycle and proliferation were determined by MTT assay and flow cytometry (FCM). The results showed that sur promoter could specifically drive the expression of double CD/TK gene in SGC-7901 cells, whereas not in the normal GES-1 cell. After using CCV and 5-FC, the growth of SGC-7901 cells was inhibited. G1 phase proportion was significantly higher in SGC-7901 cells transfected with double suicide genes than the untransfected cells. These results suggest that CD and TK double suicide genes driven by sur promoter could provide a new approach for enhancing selective suicide gene therapy of CD/5-FC for the treatment of advanced gastric carcinoma.