Impact of Bevacizumab on Experimentally Induced Endometriotic Lesions: Angiogenesis, Invasion, Apoptosis, and Cell Proli
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ORIGINAL ARTICLE
Impact of Bevacizumab on Experimentally Induced Endometriotic Lesions: Angiogenesis, Invasion, Apoptosis, and Cell Proliferation Ana Carolina Tagliatti Zani 1 & Fernando Passador Valerio 1 & Juliana Meola 1 & Alfredo Ribeiro da Silva 2 & Antonio Alberto Nogueira 1 & Francisco José Candido-dos-Reis 1 & Omero Benedicto Poli-Neto 1 & Julio Cesar Rosa-eSilva 1 Received: 21 February 2020 / Accepted: 6 May 2020 # Society for Reproductive Investigation 2020
Abstract Endometriosis is responsible for pain symptoms with great impact on the patient’s quality of life. Several medication lines have been studied aiming at its definitive treatment. Among them, angiogenesis inhibitor factors may be effective given that angiogenesis has fundamental role in the establishment and growth of endometriotic lesions. In this study, we investigated the influence of bevacizumab, anti-factor drug of endothelial growth (anti-VEGF), used at two different dosages, in experimental endometriosis induced in rats. After the induction of endometriosis lesions in rats, they were divided in 3 groups: control group, no treatment, and two other groups were treated with different dosages of the same medication for 4 weeks. At the end of the treatment, endometriotic lesions were removed and evaluated regarding area of lesions, presence of endometrial tissue in microscopy, positivity for anti-VEGF antibody in immunohistochemistry, and gene expression of Pcna, Mmp9, Tp63, and Vegfa. Bevacizumab acted by reducing the area of lesions in the groups that received medication (p = 0.002) and reducing gene expression to Tp63 in lesions (p = 0.04). There was no significant result in other evaluations. We observed that there was significant reduction of the area of lesions among groups, suggesting that bevacizumab has a positive effect on disease control. The gene expression of Tp63 was significantly lower in the group that received high dose of the drug when compared with the other two groups; therefore, we concluded that bevacizumab acts by reducing cell proliferation and differentiation in lesions, constituting a real option for treating endometriosis. Keywords Experimental endometriosis . Angiogenesis . Bevacizumab . VEGF
Introduction Endometriosis is a condition characterized by the growth of the endometrial gland and/or stroma out of the uterine cavity. It is an estrogen-dependent benign disease that occurs in 5 up to 10% of women at reproductive age [1]; it may reach from 40 to 60% among women with dysmenorrheal [2]. The disease shows diversified symptomology, ranging from acyclic pelvic pain to
* Julio Cesar Rosa-e-Silva [email protected] 1
Ribeirão Preto School of Medicine, Department of Gynecology and Obstetrics, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP 14049-900, Brazil
2
Ribeirão Preto School of Medicine, Department of Pathology and Legal Medicine, University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, SP 14049-900, Brazil
infertility [3], symptoms that have a big impact upon women’s physical, m
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