Related Experiment Video
Updated: Jun 17, 2026
Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity
Published on: December 31, 2015
Targeting pericytes with a PDGF-B aptamer in human ovarian carcinoma models
Chunhua Lu1, Mian M K Shahzad, Myrthala Moreno-Smith
1Department of Gynecologic Oncology, U.T.M.D. Anderson Cancer Center, Houston, TX, USA.
Purpose:
On the basis of the known role of platelet-derived growth factor (PDGF)-BB/PDGF receptor (PDGFR) beta in pericyte regulation, highly specific inhibitors of this target are needed. We tested the efficacy of a highly selective aptamer against PDGF-B with or without anti-VEGF therapy in ovarian cancer models.
Results:
Bevacizumab inhibited tumor growth by 45% and 48% in the HeyA8 and SKOV3ip1 models, respectively. AX102 had minimal effect on the HeyA8 model, but increased tumor growth in the SKOV3ip1 model. However, bevacizumab plus AX102 was more effective than bevacizumab alone, and resulted in 76-88% inhibition of tumor growth in both models. A longitudinal study in the HeyA8 model using bioluminescence imaging showed that combination of bevacizumab, AX102 and paclitaxel caused tumor reduction by 65% (based on bioluminescence imaging). In the HeyA8 model, MVD and PCNA counts were significantly reduced in the bevacizumab treatment groups, and pericyte coverage was significantly decreased in the AX102 treatment groups. In the SKOV3ip1 model, MVD and PCNA was significantly reduced in the bevacizumab treatment group, and even lower in the bevacizumab and AX102 combination treatment group.
Experimental Design:
The therapeutic efficacy of targeting endothelial cells (bevacizumab) and/or pericytes (PDGF-aptamer, AX102) was examined using HeyA8 and SKOV3ip1 orthotopic models of ovarian cancer metastasis. Following therapy, tumors were examined for microvessel density (MVD), proliferating cell nuclear antigen (PCNA) and vascular maturation (pericyte coverage).
Conclusions:
Dual targeting of endothelial cells and pericytes holds potential as an anti-vascular therapeutic approach in ovarian carcinoma.
Insights
Targeting both endothelial cells and pericytes with anti-VEGF therapy and a PDGF-B aptamer significantly inhibited ovarian cancer growth. This dual-targeting approach shows promise for anti-vascular therapies in ovarian carcinoma.
Area of Science:
- Oncology
- Vascular Biology
- Drug Development
Background:
- Platelet-derived growth factor (PDGF)-BB/PDGF receptor (PDGFR) beta plays a key role in pericyte regulation.
- Highly specific inhibitors targeting PDGF-B are needed for therapeutic applications.
Purpose of the Study:
- To evaluate the efficacy of a selective aptamer against PDGF-B (AX102), alone or combined with anti-VEGF therapy (bevacizumab), in ovarian cancer models.
- To assess the impact of dual targeting of endothelial cells and pericytes on tumor growth and vascularization.
Main Methods:
- Utilized HeyA8 and SKOV3ip1 orthotopic ovarian cancer metastasis models.
- Administered bevacizumab (anti-endothelial) and/or AX102 (anti-pericyte aptamer) therapy.
- Assessed tumor growth, microvessel density (MVD), proliferating cell nuclear antigen (PCNA), and pericyte coverage.
Main Results:
- Bevacizumab monotherapy inhibited tumor growth by 45-48%.
- Combination therapy (bevacizumab + AX102) achieved 76-88% tumor growth inhibition, outperforming monotherapy.
- Dual targeting significantly reduced MVD, PCNA, and pericyte coverage in both models.
Conclusions:
- Dual targeting of endothelial cells and pericytes demonstrates significant anti-tumor efficacy in ovarian cancer.
- This combination therapy represents a promising anti-vascular therapeutic strategy for ovarian carcinoma.
