Construction of a novel vector expressing Survivin-shRNA and fusion suicide gene yCDglyTK and its application in inhibiting proliferation and migration of colon cancer cells.

ABSTRACT

Despite progress achieved in cancer chemotherapy in recent decades, adverse effects remain a limiting factor for a number of patients with colorectal cancer, suggesting the requirement for novel therapeutic strategies. Gene therapy appears to be a promising strategy for treating cancer. The present study aimed to investigate the anti-tumor effect of a combined gene therapy, using Survivin downregulation by RNAi and a fusion suicide gene yCDglyTK therapy system. A triple-gene vector expressing Survivin-targeted small hairpin RNA (Survivin-shRNA) and fusion suicide gene yCDglyTK was constructed, and administered to HCT116 cells. Survivin expression decreased significantly and yCDglyTK fusion gene expression was confirmed by both reverse transcription-quantitative polymerase chain reaction and western blot analysis. Introduction of Survivin-shRNA into yCDglyTK/prodrug system eradicated colon cancer cells and induced apoptosis more effectively. Furthermore, this therapeutic system is able to inhibit the migration of HCT116 cells. These results indicate that the recombinant plasmid may serve as a novel gene therapy approach to treat colorectal carcinoma.