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 c olorectal cancers. Materials and Methods: We infected the colorectal c ancer cell lines SW620 and KM12L4, in which p53 is mutated, with the r eplication-defective adenovirus Ad5/CMV/p53 to evaluate the effects of adenovirus-mediated wild-type p53 gene transfer: Gene transduction wa s measured by cytochemical staining of cells infected with the Ad5/CMV /beta-gal virus and expression of the wildtype p53 protein in these ce lls was demonstrated by immunoblotting. Results: Significant suppressi on of in vitro cell proliferation and induction of apoptosis (as measu red by TUNEL assay labeling) were observed following Ad5/CMV/p53 infec tion. Mole importantly, similar effects were observed in vivo in an es tablished 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 for m of therapy may provide a novel approach to colorectal cancer.