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Published on: March 7, 2011
Gene therapy of prostate xenograft tumors with a p75NTR lipoplex
Jeffrey Allen1, Fatima Khwaja, Daniel Djakiew
1Department of Cell Biology, Georgetown University Medical Center, Washington DC, USA.
Abstract:
The p75neurotrophin receptor (p75NTR) has been characterized as a tumor suppressor in human prostate cancer. Ectopic re-expression of this cell surface receptor protein in prostate cancer cell lines has been shown to increase the frequency of apoptosis and concurrently reduce the rate of cellular proliferation. Since it is difficult to maintain a therapeutic level of this membrane receptor protein by systemic administration in the blood, we utilized an alternative gene therapy strategy based upon intra-tumoral injection into xenografts of PC-3 prostate tumor cells of a lipoplex containing the p75NTR gene. Administration of the p75NTR gene into subcutaneous PC-3 xenografts suppressed in a dose-dependent manner the growth of tumors. Within the gene therapy-treated tumors, re-expression of the p75NTR gene product was associated with increased apoptosis and reduced proliferation of tumor cells. These results suggest that the p75NTR may be a suitable candidate for gene therapy of prostate cancer cells.
Insights
Gene therapy using the p75 neurotrophin receptor (p75NTR) gene suppressed prostate cancer growth. Intra-tumoral injection of the p75NTR gene increased apoptosis and reduced proliferation in PC-3 xenografts.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- The p75 neurotrophin receptor (p75NTR) acts as a tumor suppressor in prostate cancer.
- Re-expression of p75NTR in prostate cancer cells increases apoptosis and reduces proliferation.
Purpose of the Study:
- To evaluate the efficacy of gene therapy for prostate cancer using intra-tumoral delivery of the p75NTR gene.
- To investigate the effects of p75NTR gene re-expression on tumor growth, apoptosis, and proliferation in vivo.
Main Methods:
- Utilized a lipoplex formulation containing the p75NTR gene for intra-tumoral injection.
- Administered the gene therapy into subcutaneous PC-3 prostate tumor xenografts in a dose-dependent manner.
- Assessed tumor growth suppression, p75NTR gene product re-expression, apoptosis frequency, and cellular proliferation rates.
Main Results:
- Intra-tumoral administration of the p75NTR gene suppressed PC-3 xenograft tumor growth in a dose-dependent manner.
- Re-expression of the p75NTR gene product was observed within treated tumors.
- Gene therapy correlated with increased apoptosis and reduced tumor cell proliferation.
Conclusions:
- The p75 neurotrophin receptor (p75NTR) holds potential as a therapeutic target for prostate cancer gene therapy.
- Intra-tumoral gene therapy with p75NTR is a viable strategy for suppressing prostate cancer growth.
- Further research into p75NTR-based gene therapy for prostate cancer is warranted.
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