Vascular endothelial growth factor receptor-2 inhibitor cediranib causes regression of endometriotic lesions in a rat model

• Published in: International journal of clinical and experimental pathology Vol. 8; no. 2; pp. 1165 - 1174
• Main Authors: Liu, Fang, Wang, Li, Zhang, Xian-Xia, Min, Shu-Yun, Liu, Yi-Xuan, Zuo, Zhi, Jin, Zhi-Xing, Zhu, Zhi-Ling
• Format: Journal Article
• Language: English
• Published: United States e-Century Publishing Corporation 01.01.2015
• Subjects: Animals; Cell Proliferation - drug effects; Disease Models, Animal; Endometriosis - drug therapy; Endometriosis - pathology; Female; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - pathology; Original; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Quinazolines - pharmacology; Quinazolines - therapeutic use; Rats; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; endometriosis; Angiogenesis; vascular endothelial growth factor receptor-2; cediranib
• ISSN: 1936-2625

Vascular endothelial growth factor (VEGF) receptor-2 plays an essential role in angiogenesis, and it also expressed in the glandular epithelium and stromal cells of ectopic endometrium. Cediranib is a protein tyrosine kinase inhibitor that potently inhibits VEGF receptor-2, but there is no study about its effects on the endometriosis. We induced endometriosis on both sides of the abdominal wall in 20 female Sprague-Dawley rats and randomly divided them into 2 groups. They were administered: cediranib 4 mg/kg/day (group 1), equal saline (group 2) for 12 days. Then, the lesion volumes were calculated, and Masson trichrome was used to detect fibrosis. Angiogenesis was evaluated by CD-31 immunohistochemistry and serum VEGF levels. Proliferation was indicated by proliferating cell nuclear antigen immunohistochemistry. Apoptosis was measured by a TUNEL assay and cleaved caspase-3 immunohistochemistry. In the treatment group, the lesion volumes were smaller (P < 0.05), and the degree of fibrosis was greater. The microvessel density was lower (P < 0.05) than control, however, serum VEGF was up-regulated by a negative feedback mechanism (P < 0.01). In addition, proliferation was significantly suppressed (P < 0.01), and apoptosis in the lesions was more obvious in the treatment group. These data indicated that cediranib can inhibit development of endometriotic lesions in rats.