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.


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. More 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 Ad5/CMV/p53.


CONCLUSIONS
This form of therapy may provide a novel approach to colorectal cancer.
Spitz
F R
FR
Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Nguyen
D
D
Skibber
J M
JM
Cusack
J
J
Roth
J A
JA
Cristiano
R J
RJ
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016923:Cell Death; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D014162:Transfection / Q000379:methods; D014183:Transplantation, Heterologous