title: Vascular endothelial growth factor receptor-2 inhibitor cediranib causes regression of endometriotic lesions in a rat model.
abstract: 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.
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University 419 Fang-Xie Road, Shanghai 200011, PR China ; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University 138 Yi-Xueyuan Road, Shanghai 200032, PR China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases 413 Zhao-Zhou Road, Shanghai 200011, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University 419 Fang-Xie Road, Shanghai 200011, PR China ; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University 138 Yi-Xueyuan Road, Shanghai 200032, PR China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases 413 Zhao-Zhou Road, Shanghai 200011, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University 419 Fang-Xie Road, Shanghai 200011, PR China ; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University 138 Yi-Xueyuan Road, Shanghai 200032, PR China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases 413 Zhao-Zhou Road, Shanghai 200011, PR China.
authors.forename: Xian-Xia
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University 419 Fang-Xie Road, Shanghai 200011, PR China ; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University 138 Yi-Xueyuan Road, Shanghai 200032, PR China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases 413 Zhao-Zhou Road, Shanghai 200011, PR China.
authors.forename: Shu-Yun
authors.initials: SY
authors.lastname: Min
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University 419 Fang-Xie Road, Shanghai 200011, PR China ; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University 138 Yi-Xueyuan Road, Shanghai 200032, PR China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases 413 Zhao-Zhou Road, Shanghai 200011, PR China.
authors.forename: Yi-Xuan
authors.initials: YX
authors.lastname: Liu
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University 419 Fang-Xie Road, Shanghai 200011, PR China ; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University 138 Yi-Xueyuan Road, Shanghai 200032, PR China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases 413 Zhao-Zhou Road, Shanghai 200011, PR China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zuo
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University 419 Fang-Xie Road, Shanghai 200011, PR China ; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University 138 Yi-Xueyuan Road, Shanghai 200032, PR China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases 413 Zhao-Zhou Road, Shanghai 200011, PR China.
authors.forename: Zhi-Xing
authors.initials: ZX
authors.lastname: Jin
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University 419 Fang-Xie Road, Shanghai 200011, PR China ; Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University 138 Yi-Xueyuan Road, Shanghai 200032, PR China ; Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases 413 Zhao-Zhou Road, Shanghai 200011, PR China.
authors.forename: Zhi-Ling
authors.initials: ZL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*; D007211:Indoles
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D040301:Vascular Endothelial Growth Factor Receptor-2; C000602029:Kdr protein, rat; C500926:cediranib; D007211:Indoles
keywords: Angiogenesis; cediranib; endometriosis; vascular endothelial growth factor receptor-2