Candido Tuany Zambroti, de Paiva Raphael Enoque Ferraz, Figueiredo Mariana Cecchetto, de Oliveira Coser Lilian, Frajácomo Silmara Cristina Lazarini, Abbehausen Camilla, Cardinalli Izilda Aparecida, Lustri Wilton Rogerio, Carvalho João Ernesto, Ruiz Ana Lucia Tasca Gois, Corbi Pedro Paulo, Lima Carmen Silvia Passos
Department of Anesthesiology, Oncology and Radiology, Faculty of Medical Sciences, University of Campinas-UNICAMP, Campinas 13083-887, SP, Brazil.
Institute of Chemistry, University of Campinas-UNICAMP, Campinas 13083-970, SP, Brazil.
Pharmaceutics. 2022 Feb 21;14(2):462. doi: 10.3390/pharmaceutics14020462.
Oxidative stress and inflammation act on skin squamous cell carcinoma (SSCC) development and progression. Curative therapy for SSCC patients is mainly based on surgical resection, which can cause various sequelae. Silver ions have in vitro activities over tumor cells, while nimesulide has antioxidant and anti-inflammatory activities. This study aimed to evaluate the effects of a silver(I) complex with nimesulide (AgNMS) incorporated in a sustained release device based on bacterial cellulose membrane, named AgNMS@BCM, on topic SSCC treatment. The antiproliferative effect of AgNMS complex was evaluated in the SCC4, SCC15 and FaDu SCC lines. AgNMS complex activity on exposure of phosphatidylserine (PS) residues and multicaspase activation were evaluated on FaDu cells by flow cytometry. The AgNMS@BCM effects were evaluated in a SSCC model induced by 7,12-dimethylbenzanthracene/12--tetradecanoyl-phorbol-13-acetate (DMBA/TPA) in mice. Toxicity and tumor size were evaluated throughout the study. AgNMS complex showed antiproliferative activity in SCC15 and FaDu lines in low to moderate concentrations (67.3 µM and 107.3 µM, respectively), and induced multicaspase activation on FaDu cells. The AgNMS@BCM did not induce toxicity and reduced tumor size up to 100%. Thus, the application of AgNMS@BCM was effective and safe in SSCC treatment in mice, and can be seen as a potential and safe agent for topic treatment of SSCC in humans.
氧化应激和炎症作用于皮肤鳞状细胞癌（SSCC）的发生和发展。SSCC患者的根治性治疗主要基于手术切除，这可能会导致各种后遗症。银离子对肿瘤细胞具有体外活性，而尼美舒利具有抗氧化和抗炎活性。本研究旨在评估基于细菌纤维素膜的缓释装置中掺入的尼美舒利银（I）配合物（AgNMS），即AgNMS@BCM，对局部SSCC治疗的效果。在SCC4、SCC15和FaDu SCC细胞系中评估了AgNMS配合物的抗增殖作用。通过流式细胞术在FaDu细胞上评估了AgNMS配合物对磷脂酰丝氨酸（PS）残基暴露和多半胱天冬酶激活的活性。在由7,12-二甲基苯并蒽/12-十四酰佛波醇-13-乙酸酯（DMBA/TPA）诱导的小鼠SSCC模型中评估了AgNMS@BCM的效果。在整个研究过程中评估了毒性和肿瘤大小。AgNMS配合物在低至中等浓度（分别为67.3 μM和107.3 μM）下对SCC15和FaDu细胞系显示出抗增殖活性，并诱导FaDu细胞上的多半胱天冬酶激活。AgNMS@BCM未诱导毒性，并且使肿瘤大小减少了100%。因此，AgNMS@BCM在小鼠SSCC治疗中应用有效且安全，可被视为人类局部治疗SSCC的一种潜在且安全的药物。
