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Updated: Feb 16, 2026
Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-Like Cells using the Three-Dimensional Co-Culture System, NICO-1
Published on: December 5, 2020
PDGFB as a vascular normalization agent in an ovarian cancer model treated with a gamma-secretase inhibitor
Maria C Pazos1, Gonzalo Sequeira1, Sebastian Bocchicchio1
1Instituto de Biología y Medicina Experimental (IByME-CONICET), Vuelta de Obligado, Buenos Aires, Argentina.
Abstract:
Ovarian cancer is the fifth leading cause of cancer-related deaths in women. In the past 20 years, the canonical types of drugs used to treat ovarian cancer have not been replaced and the survival rates have not changed. These facts show the clear need to find new therapeutic strategies for this illness. Thus, the aim of the present study was to investigate the effect of a gamma-secretase inhibitor (DAPT) in combination with the Platelet-derived growth factor B (PDGFB) on an ovarian cancer xenograft model. To achieve this goal, we analyzed the effect of the administration of DAPT alone and the co-administration of DAPT and recombinant PDGFB on parameters associated with tumor growth and angiogenesis in an orthotopic experimental model of ovarian cancer. We observed that the dose of DAPT used was ineffective to reduce ovarian tumor growth, but showed anticancer activity when co-administered with recombinant PDGFB. The administration of PDGFB alone normalized tumor vasculature by increasing periendothelial coverage and vascular functionality. Interestingly, this effect exerted by PDGFB was also observed in the presence of DAPT. Our findings suggest that PDGFB is able to improve tumor vascularity and allows the anticancer action of DAPT in the tumor. We propose that this therapeutic strategy could be a new tool for ovarian cancer treatment and deserves further studies.
Insights
Combining Platelet-derived growth factor B (PDGFB) with a gamma-secretase inhibitor (DAPT) shows promise for ovarian cancer treatment. PDGFB improved tumor vascularity, enabling DAPT
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Ovarian cancer remains a leading cause of cancer deaths in women.
- Current treatments have stagnated, highlighting the need for novel therapeutic strategies.
- There is a critical unmet need for effective ovarian cancer therapies.
Purpose of the Study:
- To investigate the combined therapeutic effect of a gamma-secretase inhibitor (DAPT) and Platelet-derived growth factor B (PDGFB) in an ovarian cancer model.
- To evaluate the impact of DAPT and PDGFB on tumor growth and angiogenesis.
- To determine if PDGFB can enhance the efficacy of DAPT in ovarian cancer.
Main Methods:
- Utilized an orthotopic experimental model of ovarian cancer xenografts.
- Administered DAPT alone and in combination with recombinant PDGFB.
- Assessed tumor growth, angiogenesis, vascular normalization, and periendothelial coverage.
Main Results:
- DAPT alone did not significantly reduce ovarian tumor growth at the tested dose.
- Co-administration of DAPT with PDGFB demonstrated anticancer activity.
- PDGFB alone normalized tumor vasculature, improving vascular functionality and periendothelial coverage.
- PDGFB's vascular normalizing effect was maintained in the presence of DAPT.
Conclusions:
- PDGFB enhances tumor vascularity, which is crucial for enabling the anticancer action of DAPT.
- The combination of PDGFB and DAPT represents a potential new therapeutic strategy for ovarian cancer.
- Further research is warranted to explore this combination therapy for ovarian cancer treatment.
