Related Experiment Video
Updated: Jul 6, 2026
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
Inhibition of intra-abdominal adhesion formation with the angiogenesis inhibitor sunitinib
Sendia Kim1, Sang Lee, Arin K Greene
1Department of Surgery, Children's Hospital Boston Harvard Medical School, Boston, Massachusetts 02115, USA.
Objective:
To determine the effects of sunitinib, a vascular endothelial growth factor receptor 2 (VEGFR-2) antagonist, on intra-abdominal adhesions.
Background:
In the United States, complications from adhesions cost $1 billion and account for 846,000 inpatient days annually. Endothelial mitogens, such as VEGF, are up-regulated during adhesion formation. Sunitinib, a tyrosine kinase inhibitor with antiangiogenic and antitumor properties, may prevent or reduce postoperative abdominal adhesions by VEGFR-2 inhibition.
Methods:
The cecum of 37 mice were abraded to promote adhesion formation and a silicone patch was sutured to the abdominal wall. The mice were randomized into two groups: Group 1 was treated with sunitinib in methylcellulose by oral gavage daily and Group 2 (control) received methylcellulose alone. After 10 d the mice were sacrificed and intra-abdominal adhesions were scored. The experiment was then repeated and mice were sacrificed on postoperative day 30 to assess the long-term effects of sunitinib.
Results:
All 19 control mice developed intra-abdominal adhesions. Six of the 18 (33.3%) mice in the treatment group were adhesion-free. Collectively, the sunitinib-treated mice had a lower adhesion score [2.0 (IQR 0.0-5.0; range 0-8.0)] than the control group [5.0 (IQR 3.0-8.0; range 2.0-10.0) (P = 0.002)]. Long-term results were consistent with this finding [sunitinib 0.0 (IQR 0.0-3.0; range 0-7) and control 6.0 (IQR 3.0-7.0; range 0-12) (P = 0.049)].
Conclusion:
Adhesion formation is angiogenesis-dependent and is in part mediated through VEGFR-2. Sunitinib, a VEGFR-2 antagonist, significantly reduces adhesion formation in a murine model. Antiangiogenic therapy may be an efficacious strategy to prevent or treat adhesions after intra-abdominal procedures.
Insights
Sunitinib, a vascular endothelial growth factor receptor 2 (VEGFR-2) antagonist, significantly reduced intra-abdominal adhesions in a murine model. This antiangiogenic therapy shows promise for preventing postoperative adhesions.
Area of Science:
- Surgical research
- Oncology
- Vascular biology
Background:
- Abdominal adhesions cause significant morbidity and healthcare costs in the US.
- Vascular Endothelial Growth Factor (VEGF) is upregulated during adhesion formation.
- Sunitinib, a tyrosine kinase inhibitor, targets VEGF signaling and may inhibit adhesion development.
Purpose of the Study:
- To evaluate the efficacy of sunitinib in preventing or reducing intra-abdominal adhesions.
- To investigate the role of VEGFR-2 antagonism in adhesion formation.
Main Methods:
- A murine model with induced cecal adhesions was used.
- Mice were treated with sunitinib or a placebo (methylcellulose) via oral gavage.
- Adhesion formation was assessed at 10 and 30 days post-surgery.
Main Results:
- 33.3% of sunitinib-treated mice were adhesion-free compared to 0% in controls.
- Sunitinib treatment significantly reduced adhesion scores at both 10 days (P=0.002) and 30 days (P=0.049).
- Adhesion scores were lower in the sunitinib group (2.0) versus controls (5.0) at day 10.
Conclusions:
- Intra-abdominal adhesion formation is dependent on angiogenesis and mediated by VEGFR-2.
- Sunitinib effectively reduces adhesion formation in a preclinical model.
- Antiangiogenic therapy represents a potential strategy for managing postoperative adhesions.
Related Concept Videos
01:10Mechanism of Angiogenesis
01:24Regulation of Angiogenesis and Blood Supply