Abstract
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.
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The funding for this research was provided by the Louisiana Board of Regents, LEQSF (2004-07)-RD-A-28 (WTG, XZ), and the Louis Stokes-Louisiana Alliance for Minority Participation (LS-LAMP), Tulane campus program (CT).
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Zhang, X., Turner, C. & Godbey, W.T. Comparison of Caspase Genes for the Induction of Apoptosis Following Gene Delivery. Mol Biotechnol 41, 236–246 (2009). https://doi.org/10.1007/s12033-008-9133-9
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DOI: https://doi.org/10.1007/s12033-008-9133-9