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Published on: August 14, 2016
An Epidermal Growth Factor Motif of Developmental Endothelial Locus 1 Protein Inhibits Efficient Angiogenesis in
Hisataka Kitano1, Atsushi Mamiya1, Tomomi Ishikawa1
1Divisions of Oral Surgery, Nihon University School of Medicine, Tokyo, Japan.
Background:
Cancer gene therapy using a nonviral vector is expected to be repeatable, safe, and inexpensive, and to have longterm effectiveness. Gene therapy using the E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has been shown to improve prognosis in a mouse transplanted tumor model.
Objective:
In this study, we examined how this treatment affects angiogenesis in mouse transplanted tumors.
Materials And Methods:
Mouse transplanted tumors (SCCKN human squamous carcinoma cell line) were injected locally with a nonviral plasmid vector encoding E3C1 weekly. Histochemical analysis of the transplanted tumors was then performed to assess the effects of E3C1 on prognosis.
Results:
All mice in the control group had died or reached an endpoint within 39 days. In contrast, one of ten mice in the E3C1 group had died by day 39, and eight of ten had died or reached an endpoint by day 120 (p < 0.01). Enhanced apoptosis in tumor stroma was seen on histochemical analyses, as was inhibited tumor angiogenesis in E3C1-treated mice. In addition, western blot analysis showed decreases in active Notch and HEY1 proteins.
Conclusion:
These findings indicate that cancer gene therapy using a nonviral vector encoding E3C1 significantly improved life-span by inhibiting tumor angiogenesis.
Insights
Nonviral cancer gene therapy using the E3C1 domain of developmental endothelial locus-1 (Del1) significantly extended lifespan in mice. This approach inhibited tumor angiogenesis and enhanced apoptosis, offering a promising, safe, and repeatable treatment strategy.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Nonviral gene therapy offers a repeatable, safe, and cost-effective approach for cancer treatment with potential for long-term effectiveness.
- The E3 and C1 (E3C1) domain of developmental endothelial locus-1 (Del1) has demonstrated therapeutic potential in a mouse transplanted tumor model.
Purpose of the Study:
- To investigate the impact of E3C1 gene therapy on angiogenesis in mouse transplanted tumors.
- To evaluate the effects of E3C1 treatment on tumor prognosis and survival rates.
Main Methods:
- Mouse transplanted tumors (SCCKN human squamous carcinoma cell line) were treated with a nonviral plasmid vector encoding E3C1 weekly.
- Histochemical and Western blot analyses were performed to assess tumor apoptosis, angiogenesis, and protein expression.
Main Results:
- E3C1 treatment significantly improved survival rates compared to the control group (p < 0.01).
- Histochemical analysis revealed enhanced apoptosis in tumor stroma and inhibited tumor angiogenesis in E3C1-treated mice.
- Western blot analysis indicated decreased levels of active Notch and HEY1 proteins.
Conclusions:
- Nonviral gene therapy utilizing the E3C1 domain is a viable strategy for cancer treatment.
- E3C1 effectively inhibits tumor angiogenesis, leading to improved lifespan.
- This therapeutic approach demonstrates significant potential for enhancing cancer patient prognosis.
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