Cyclooxygenase-2 (COX-2), the enzyme that catalyzes the conversion of arachidonic acid to prostaglandin H2 in the biosynthesis process of prostanoids, is overexpressed in various cancer types, such as breast, esophagus, gastric, colon, prostate, cervical, liver as well as bladder while is undetectable or weak in normal tissues. This tumor-specific expression of COX-2 implies that COX-2 promoter can be used to target the expression of delivered plasmids to such carcinomas.

In our present study, the murine COX-2 promoter was utilized to target the expression of delivered pro-apoptotic genes to the established cell line MB49 derived from murine bladder transitional cell carcinoma in vitro. The pro-apoptotic genes, delivered via the polycation poly (ethylenimine) (PEI) in unmodified forms, coded for inducible forms of caspases1, 3 and 9 (icasps 1, 3 & 9), which remained inactive until the administration of a chemical inducer of dimerization post-transcriptionally. Different dosage concentration of the PEI/icasps complexes were tested, and results demonstrated that the 1X dose concentration of PEI/ icaps3/icasp9 was the most effective one which resulted in only 51.7% of the cell viability compared to the negative controls. This same promoter-targeted gene therapy method was also studied on the CT26.CL25 (established cell line from colon cancer) in vitro with similar results. Moreover, the therapeutic result of the caspases 3 & 9 were compared to that of granzyme B.

The delivery of pro-apoptotic genes that coded for inducible forms of caspases 3 & 9, with post-transcriptional activation, can be used to significantly prompt the cell apoptosis process of the MB49 and CT25.CL26 cells. This gene therapy method can be further utilized to treat bladder and colon cancer in mice in vivo. Furthermore, because of the up-regulation of COX-2 expression seen in other carcinomas, this treatment regimen could have wide applicability to an array of cancers.