Effect Of Bevacizumab On Growth Of Human Nasal Polyposis In Vitro; An Off-Label Use Of Anti-Angiogenic Agent For Nasal Polyposis Treatment

Drug Design, Development and Therapy Dovepress open access to scientific and medical research Drug Design, Development and Therapy downloaded from https://www.dovepress.com/ by 88.198.20.149 on 01-Oct-2019 For personal use only. Open Access Full Text Article ORIGINAL RESEARCH Effect Of Bevacizumab On Growth Of Human Nasal Polyposis In Vitro; An Off-Label Use Of Anti-Angiogenic Agent For Nasal Polyposis Treatment This article was published in the following Dove Press journal: Drug Design, Development and Therapy Shadman Nemati 1 Faeze Keihanian 2,3 Amin Saeidinia 4,5 Mahdi Bakhshaei 6 1 Rhino-sinus, Ear, and Skull Base Diseases Research Center, Guilan University of Medical Sciences, Rasht, Iran; 2Cardiology Department, Imam Reza & Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; 3Pharmaceutical Research Division, Booali Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 4Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran; 5Pharmaceutical Research Division, Booali Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; 6Faculty of Medicine, Ear, Nose and Throat Department, Mashhad University of Medical Sciences, Mashhad, Iran Introduction: Nasal polyposis (NP) is a frequent problem during adulthood. Treatment of NP is primarily based on drugs, such as oral or topical steroids and in some types, by surgery. Despite of available therapeutic options for NP, recurrence after polypectomy is found. Vascular endothelial growth factor (VEGF) is a known factor involved in NP. Bevacizumab is a monoclonal antibody, which acts against VEGF. Aim: Regarding the availability of bevacizumab and its use in ophthalmic off-label application, in this study, we hypothesized that it could be a choice of non-invasive treatment. The researchers aimed at evaluating the use of bevacizumab in vitro on the growth of NP. Materials and methods: In this experimental study, the researchers used eight non-allergic NP tissues from patients admitted for polypectomy clinic of Imam Reza Hospital, Mashhad. Tissues were cultured in DMEM medium based on standard protocols in the presence or absence of bevacizumab (10 to 250 μM) then incubated. The mean of the responses was reported. The level of VEGF and MTT test for NP epithelial cell viability were determined for each group. Data were analyzed using the SPSS software. Results: The researchers demonstrated that bevacizumab leads to a decrease in the level of VEGF (the most common cause of angiogenesis in NP) in media culture of NP, dosedependently (P<0.001). The highest mean was related to the 10-μM group and the least mean was related to the 250-μM group. In MTT test after 5 days, it was shown that the percentage of viable epithelial NP cells (due to apoptosis) was decreased dose-dependently and could lead to resolving NP tissue (P<0.001), significantly. Conclusion: This study showed that bevacizumab could help decrease the growth of NP tissue dose-dependently in organ culture in vitro by inhibiting VEGF. It seems that bevacizumab could be a good candidate for the treatment of non-allergic NP. Keywords: nasal polyposis, non-allergic polyps, bevacizumab, Avastin, in vitro study Introduction Correspondence: Amin Saeidinia Faculty of Medicine, Mashhad University Complex, Azadi Square, Mashhad 9177948564, Iran Tel +98 511 9119451607 Email 3383 submit your manuscript | www.dovepress.com Drug Design, Development and Therapy 2019:13 3383–3389 DovePress © 2019 Nemati et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms. php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://doi.org/10.2147/DDDT.S219724 Powered by TCPDF (www.tcpdf.org) The prevalence of nasal polyposis (NP) during adulthood is between 1% and 4% and in children, except in cases of cystic fibrosis, this is lower. It usually involves patients between 30 and 60 years old and is two to four times more frequent in males than females.1,2 Furthermore, NP is a chronic inflammatory disorder of nasal and paranasal sinuses mucosal membrane with unknown etiology. It is characterized by inflammatory edematous mucus mass that makes a wide or narrow stalk.3–5 Dovepress Drug Design, Development and Therapy downloaded from https://www.dovepress.com/ by 88.198.20.149 on 01-Oct-2019 For personal use only. Nemati et al NP tissue is covered by pseudo-stratified epithelium except some parts, which had squamous cells and basement membrane thickness.4 It is a multifactorial disorder that is associated with infection, inflammation without infection, and genetic and anatomic anomalies. There are some conditions related to NP, such as allergic and nonallergic rhinitis, fungal allergic sinusitis, aspirin intolerance, asthma, Churg-Strauss syndrome, cystic fibrosis, Kartagener syndrome, and primary ciliary dyskinesia.4 It has been determined that eosinophil infiltration, fibronectin expression, and edematous histology are associated with the size of NP. It has been indicated that eosinophil and fibronectin interaction may have a role in edema formation and lead to the growth of NP.6 Moreover, vascular endothelial growth factor (VEGF) is severely increased in NP mucosa.7 Precursor mRNA of tumor growth factor (TGF) and fibroblast growth factor (FGF) are increased in NP tissues. Immunohistochemistry analysis indicated that TGF-β is accumulated in extra-cellular matrix and NP stroma, beside eosinophils.8 It has been demonstrated that TGF-α, TGF-β, FGF, and epidermal growth factor induced the expression of VEGF, which is a known and strong factor in endothelial cell mitosis and vascular permeability.9 In another study, it was shown that in the nasal cavity, VEGF expression leads to angiogenesis and an increase in the vascular permeability.10 Furthermore, NP treatment is primarily oral or topical nasal steroids. Although in some cases that surgery is necessary, aggressive medical treatment is needed before and after surgery.11 The goal of treatment in NP is maintaining ventilation and discharge of sinuses, beside preventing its recurrence.4 Patients with abnormal endoscopic findings are tended to recurrence and will need greater surgical interventions in the future.3 Although there are many available options for treatment of NP, about 40% of patients that undergo polypectomy will encounter recurrence and need to re-surgery.2 It has been demonstrated that VEGF has an important role in angiogenesis of nasa (...truncated)