Comparison of caspase genes for the induction of apoptosis following gene delivery.

The polycation poly(ethylenimine) (PEI) was used to deliver the plasmids coding for various combinations of caspases to Cox-2 overexpressing cancer cell lines. It was found that the expression of the delivered genes, controlled by the Cox-2 promoter, correlated with the expression of the endogenous Cox-2 gene in each cell line in a relatively linear manner. Among the various caspase combination regimens, the combination of caspase 3 plus caspase 9 proved to be the most effective because of an apparent synergy between the two gene products, and produced phosphatidylserine flipping in addition to fragmentation of genomic DNA. Caspase 1 appeared to work independently of either caspases 3 or 9, as no synergistic effect was observed. Transfections with genes coding for granzyme B and caspase 8 yielded a lesser amount of cell death. The delivery of a combination of caspase genes could be readily moved to in vivo research of bladder and colon cancer treatments, and holds great applicability to a wide array of additional tumor types.