In vivo adenovirus-mediated p53 tumor suppressor gene therapy for colorectal cancer

Background: The p53 tumor suppressor gene is altered in up to 70% of colorectal cancers. Materials and Methods: We infected the colorectal cancer cell lines SW620 and KM12L4, in which p53 is mutated, with the replication-defective adenovirus Ad5/CMV/p53 to evaluate the effects of adenovirus-mediated wild-type p53 gene transfer: Gene transduction was measured by cytochemical staining of cells infected with the Ad5/CMV/beta-gal virus and expression of the wildtype p53 protein in these cells was demonstrated by immunoblotting. Results: Significant suppression of in vitro cell proliferation and induction of apoptosis (as measured by TUNEL assay labeling) were observed following Ad5/CMV/p53 infection. Mole importantly, similar effects were observed in vivo in an established nude mouse subcutaneous tumor model; significant suppression of tumor growth (60% - 70%) and induction of apoptosis were observed following intratumoral injections of AdS/CMV/p53. Conclusion: This form of therapy may provide a novel approach to colorectal cancer.