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Proapoptotic and antitumor activities of adenovirus-mediated p202 gene transfer
Yi Ding1, Yong Wen, Bill Spohn
1Departments of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Purpose And Experimental Design:
p202, a mouse IFN-inducible protein, is a member of the 200-amino acid repeat family. Enforced p202 expression in stable cancer cell lines resulted in growth inhibition in vitro and tumor suppression in vivo. However, to study the immediate effect of p202 and test the potential efficacy of p202 treatment, an efficient gene delivery system for p202 is required. For these purposes, an adenoviral vector expressing the p202 gene (Ad-p202) was generated. We examined the effects of Ad-p202 infection on human breast cancer cells. Furthermore, we tested the efficacy of Ad-p202 treatment on breast and pancreatic cancer xenograft models.
Results:
We found that Ad-p202 infection induces growth inhibition and sensitizes the otherwise resistant cells to tumor necrosis factor alpha-induced apoptosis. In addition, we demonstrated for the first time that Ad-p202 infection induces apoptosis and that activation of caspases is required for the full apoptotic effect. More importantly, we showed the efficacy of Ad-p202 treatment on breast cancer xenograft models, and this antitumor effect correlated well with enhanced apoptosis in Ad-p202-treated tumors.
Conclusions:
We conclude that Ad-p202 is a potent growth-inhibitory, proapoptotic, and tumor-suppressing agent. Ad-p202 may be further developed into an efficient therapeutic agent for human cancer gene therapy.
Insights
Adenoviral vector-mediated p202 gene delivery (Ad-p202) inhibits cancer cell growth and induces apoptosis. Ad-p202 demonstrates significant antitumor efficacy in xenograft models, suggesting potential for cancer gene therapy.
Area of Science:
- Molecular biology
- Cancer research
- Gene therapy
Background:
- p202, an IFN-inducible protein, inhibits cancer cell growth and tumor progression.
- An efficient gene delivery system is needed to study p202's immediate effects and therapeutic potential.
Purpose of the Study:
- To generate an adenoviral vector expressing p202 (Ad-p202).
- To examine Ad-p202 effects on human breast cancer cells.
- To test Ad-p202 efficacy in breast and pancreatic cancer xenograft models.
Main Methods:
- Adenoviral vector construction for p202 gene delivery.
- In vitro studies on human breast cancer cell lines.
- In vivo efficacy testing using xenograft models.
Main Results:
- Ad-p202 infection inhibited cancer cell growth and sensitized cells to TNF-alpha-induced apoptosis.
- Ad-p202 induced apoptosis, requiring caspase activation.
- Ad-p202 treatment showed significant antitumor effects in xenograft models, linked to increased apoptosis.
Conclusions:
- Ad-p202 is a potent agent for inhibiting growth, inducing apoptosis, and suppressing tumors.
- Ad-p202 holds promise as a therapeutic agent for human cancer gene therapy.