title: Effects of Pazopanib, Sunitinib, and Sorafenib, Anti-VEGF Agents, on the Growth of Experimental Endometriosis in Rats.
abstract: We aimed to compare the effects of pazopanib, sunitinib, and sorafenib on endometriotic tissue morphology and histological characteristics as well as ovarian reserve in a rat model. Experimental endometriosis was established in 32 rats. They were randomly divided into 4 groups (8 rats for each group) to administer study drugs: pazopanib, sunitinib, sorafenib, and normal saline. Histological examination with hematoxylin and eosin staining to determine endometriosis score and immunostaining with primary vascular endothelial growth factor (VEGF), CD117, and Bax antibodies were performed. Bilateral ovaries excised to determine the ovarian follicle number. The endometriosis score was significantly reduced by pazopanib compared to other study drugs and by sunitinib compared to sorafenib and normal saline (P < .05). Sorafenib did not affect endometriosis score (P > .05). The VEGF score was significantly decreased similarly by pazopanib, sunitinib, and sorafenib compared to normal saline (P < .05). The CD117 score was reduced by pazopanib and sunitinib similarly compared to both sorafenib and normal saline that provided similar effect on the score (P < .05). The Bax scores of all the groups were found similar (P > .05). No study drugs caused meaningful change in the ovarian follicle number (P > .05). Pazopanib reduces the growth of endometriotic implants. This effect may be related to the suppressive effect of pazopanib on the endometriotic tissue expressions of VEGF and CD117 but not Bax. The study drugs do not affect ovarian reserve. The inconsistent effects of study drugs regarding study parameters require further studies to elucidate the molecular bases of their effects on the growth of endometriotic implants.
authors.affiliation: Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, Sivas, Turkey dr_caglaryildiz@yahoo.com.tr.
authors.forename: Caglar
authors.initials: C
authors.lastname: Yildiz
authors.affiliation: Department of Medical Oncology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Turgut
authors.initials: T
authors.lastname: Kacan
authors.affiliation: Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Ozlem Bozoklu
authors.initials: OB
authors.lastname: Akkar
authors.affiliation: Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Savas
authors.initials: S
authors.lastname: Karakus
authors.affiliation: Department of Internal Medicine, Sivas Numune Hospital, Sivas, Turkey.
authors.forename: Selen Baloglu
authors.initials: SB
authors.lastname: Kacan
authors.affiliation: Department of Pathology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Hatice
authors.initials: H
authors.lastname: Ozer
authors.affiliation: Department of Obstetrics and Gynecology, Cumhuriyet University School of Medicine, Sivas, Turkey.
authors.forename: Ali
authors.initials: A
authors.lastname: Cetin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005260:Female; D007191:Indazoles; D007211:Indoles / Q000494:pharmacology*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D065851:Ovarian Reserve; D010671:Phenylurea Compounds / Q000494:pharmacology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D013449:Sulfonamides / Q000494:pharmacology*; D000077210:Sunitinib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; C494828:Bax protein, rat; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein; C467498:vascular endothelial growth factor A, rat; D009536:Niacinamide; C516667:pazopanib; D000077157:Sorafenib; D019009:Proto-Oncogene Proteins c-kit; D000077210:Sunitinib
keywords: anti-VEGF; endometriosis; ovarian reserve; pazopanib; sorafenib; sunitinib