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In vivo adenovirus-mediated p53 tumor suppressor gene therapy for colorectal cancer
F R Spitz1, D Nguyen, J M Skibber
1Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
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. 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.
Conclusion:
This form of therapy may provide a novel approach to colorectal cancer.
Insights
Adenovirus-mediated wild-type p53 gene transfer suppressed colorectal cancer cell proliferation and induced apoptosis in vitro and in vivo. This gene therapy shows promise for treating colorectal cancer.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- The p53 tumor suppressor gene is frequently altered in colorectal cancers, representing a significant therapeutic target.
- Mutations in p53 are common in colorectal cancer cell lines, necessitating strategies to restore wild-type p53 function.
Purpose of the Study:
- To evaluate the efficacy of adenovirus-mediated wild-type p53 gene transfer in colorectal cancer.
- To assess the impact of restoring p53 function on cancer cell proliferation and apoptosis.
Main Methods:
- Infection of colorectal cancer cell lines (SW620, KM12L4) with replication-defective adenovirus (Ad5/CMV/p53).
- Measurement of gene transduction using cytochemical staining (Ad5/CMV/beta-gal).
- Demonstration of wild-type p53 protein expression via immunoblotting.
Main Results:
- Ad5/CMV/p53 infection significantly suppressed in vitro cell proliferation and induced apoptosis in colorectal cancer cells.
- Intratumoral injections of Ad5/CMV/p53 in a nude mouse model led to significant tumor growth suppression (60%-70%) and apoptosis induction.
Conclusions:
- Adenovirus-mediated wild-type p53 gene transfer demonstrates potent anti-cancer effects in colorectal cancer models.
- This gene therapy approach offers a novel therapeutic strategy for colorectal cancer treatment.