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Updated: Jul 31, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Simultaneous targeting of VEGF message and VEGF receptor signaling as a therapeutic anticancer approach
Wenyin Shi1, Dietmar W Siemann
1Department of Radiation Oncology, Shands Cancer Center, University of Florida, Gainesville, FL 32610, USA. wshi@ufl.edu
Background:
Vascular endothelial growth factor (VEGF) is one of the most important factors involved in tumor angiogenesis.
Materials And Methods:
Antisense phosphorothiolate oligodeoxynucleotides (PS-ODNs) were used to reduce VEGF production while the small molecule PD0203359-0002 (PD203359) was used to inhibit VEGF/bFGF receptor tyrosine kinase activity.
Results:
PD203359 exposure was found to profoundly impair the growth of human endothelial cells (HMVEC-L) at doses 20-fold less than those affecting human renal cell carcinoma (Caki-1) cell growth. In vivo, treatment with PD203359 inhibited tumor cell-induced angiogenesis and resulted in a significant tumor growth delay. Treatment with VEGF antisense PS-ODNs also significantly increased the time for tumors to grow to five times the starting size. Most importantly, when the PD203359 and VEGF antisense treatments were combined, a greater antitumor response than could be achieved with either therapy alone was observed.
Conclusion:
Simultaneously targeting VEGF production and VEGF receptor signaling enhances the anticancer efficacy of either therapy alone.
Insights
Combining therapies targeting vascular endothelial growth factor (VEGF) production and receptor signaling significantly enhances antitumor responses. This dual approach improves efficacy compared to single-agent treatments for cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Vascular endothelial growth factor (VEGF) is a critical regulator of tumor angiogenesis.
- VEGF signaling pathways are key targets in cancer therapy.
Purpose of the Study:
- To investigate the combined efficacy of inhibiting VEGF production and VEGF receptor tyrosine kinase activity.
- To evaluate the synergistic effects of dual-targeted therapy on tumor growth and angiogenesis.
Main Methods:
- Utilized antisense phosphorothiolate oligodeoxynucleotides (PS-ODNs) to reduce VEGF production.
- Employed the small molecule PD0203359-0002 (PD203359) to inhibit VEGF/bFGF receptor tyrosine kinase activity.
- Assessed the impact of individual and combined treatments on human endothelial cell proliferation and in vivo tumor growth.
Main Results:
- PD203359 demonstrated potent inhibition of endothelial cell growth at low doses.
- Both PD203359 and VEGF antisense PS-ODNs significantly delayed tumor growth in vivo.
- Combined treatment yielded a superior antitumor response compared to monotherapy.
Conclusions:
- Simultaneous targeting of VEGF production and receptor signaling amplifies anticancer efficacy.
- Combination therapy represents a promising strategy for enhancing cancer treatment outcomes.
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