Related Experiment Videos
Gene therapy for pancreatic cancer using an adenovirus vector encoding soluble flt-1 vascular endothelial growth
Tohru Hoshida1, Makoto Sunamura, Dan G Duda
1Division of Advanced Science and Technology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Introduction:
Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. The soluble form of flt-1 VEGF receptor inhibits VEGF activity in a dominant-negative manner.
Aim:
This study demonstrated the regional tumor suppression effect of adenovirus-mediated soluble flt-1 in human pancreatic cancer cells.
Methodology:
The VEGF expression level was examined in nine cell lines. Panc-1 and PK-8 were used as lower- and higher-VEGF-producing cell lines, respectively. The in vitro proliferation of cancer cells infected with adenovirus vectors encoding soluble flt-1 (Adsflt) and control vectors (AdLacZ) was not different. To assess the in vivo tumor growth suppression, cancer cells were inoculated subcutaneously in SCID mice. Adsflt, AdLacZ, or vehicle was injected directly into the tumors. The early process of tumor angiogenesis in a dorsal skinfold chamber was monitored by intravital microscopy.
Results:
In both Panc-1 cells and PK-8 cells, the tumor growth of the Adsflt-treated group was significantly suppressed. The microvessel density, revealed by CD31 immunostaining, was also significantly lower in the Adsflt-treated group. Apoptosis index was higher in the Adsflt group. Immunofluorescence staining revealed the expression of VEGF not only in cancer cells but also in tumor stromal cells. Wild-type cells and AdLacZ-infected cells prompted strong tumor angiogenesis, whereas Adsflt-infected cells failed to exert such an effect.
Conclusion:
These results indicate that antiangiogenic gene therapy using soluble flt-1 might be an effective approach for pancreatic cancer treatment.
Insights
Adenovirus-mediated soluble flt-1 gene therapy effectively suppressed pancreatic tumor growth and angiogenesis in mice. This approach shows promise for treating pancreatic cancer by inhibiting vascular endothelial growth factor (VEGF).
Area of Science:
- Oncology
- Gene Therapy
- Cancer Research
Background:
- Vascular endothelial growth factor (VEGF) is crucial for tumor angiogenesis.
- Soluble flt-1 receptor inhibits VEGF activity.
- Pancreatic cancer is a significant health concern requiring novel treatments.
Purpose of the Study:
- To evaluate the regional tumor suppression effect of adenovirus-mediated soluble flt-1 in human pancreatic cancer cells.
- To assess the impact of soluble flt-1 on tumor angiogenesis and growth in vivo.
Main Methods:
- Adenovirus vectors encoding soluble flt-1 (Adsflt) and control vectors (AdLacZ) were used.
- Human pancreatic cancer cell lines (Panc-1, PK-8) were infected and xenografted in SCID mice.
- Tumor growth, microvessel density, and apoptosis were analyzed.
- Intravital microscopy monitored early tumor angiogenesis.
Main Results:
- Adsflt significantly suppressed tumor growth in both cell lines.
- Microvessel density was significantly reduced in Adsflt-treated tumors.
- Apoptosis index increased, and tumor angiogenesis was inhibited by Adsflt.
Conclusions:
- Adenovirus-mediated soluble flt-1 demonstrates significant anti-tumor and anti-angiogenic effects in pancreatic cancer models.
- Soluble flt-1 gene therapy is a potential therapeutic strategy for pancreatic cancer.