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抗炎药物与子宫颈癌细胞:甲氯芬那酸的抗肿瘤作用。

Anti-inflammatory drugs and uterine cervical cancer cells: Antineoplastic effect of meclofenamic acid.

作者信息

Soriano-Hernandez Alejandro D, Madrigal-Pérez Daniela, Galvan-Salazar Hector R, Martinez-Fierro Margarita L, Valdez-Velazquez Laura L, Espinoza-Gómez Francisco, Vazquez-Vuelvas Oscar F, Olmedo-Buenrostro Bertha A, Guzman-Esquivel Jose, Rodriguez-Sanchez Iram P, Lara-Esqueda Agustin, Montes-Galindo Daniel A, Delgado-Enciso Ivan

机构信息

School of Medicine, University of Colima, Colima, Colima 28030, Mexico ; Cancerology State Institute, Colima State Health Services, Colima, Colima 28000, Mexico.

School of Medicine, University of Colima, Colima, Colima 28030, Mexico.

出版信息

Oncol Lett. 2015 Oct;10(4):2574-2578. doi: 10.3892/ol.2015.3580. Epub 2015 Aug 7.

Abstract

Uterine cervical cancer (UCC) is one of the main causes of cancer-associated mortality in women. Inflammation has been identified as an important component of this neoplasia; in this context, anti-inflammatory drugs represent possible prophylactic and/or therapeutic alternatives that require further investigation. Anti-inflammatory drugs are common and each one may exhibit a different antineoplastic effect. As a result, the present study investigated different anti-inflammatory models of UCC in vitro and in vivo. Celecoxib, sulindac, nimesulide, dexamethasone, meclofenamic acid, flufenamic acid and mefenamic acid were tested in UCC HeLa, VIPA, INBL and SiHa cell lines. The cytotoxicity of the drugs was evaluated . Celecoxib, sulindac, nimesulide, mefenamic acid and flufenamic acid presented with slight to moderate toxicity (10-40% of cell death corresponding to 100 µM) in certain cell lines, while meclofenamic acid exhibited significant cytotoxicity in all essayed cell lines (50-90% of cell death corresponding to 100 µM). The meclofenamic acid was tested in murine models (immunodeficient and immunocompetent) of UCC, which manifested a significant reduction in tumor growth and increased mouse survival. It was demonstrated that of the evaluated anti-inflammatory drugs, meclofenamic acid was the most cytotoxic, with a significant antitumor effect in murine models. Subsequent studies are necessary to evaluate the clinical utility of this drug.

摘要

子宫颈癌(UCC)是女性癌症相关死亡的主要原因之一。炎症已被确定为这种肿瘤形成的一个重要组成部分;在这种情况下,抗炎药物是可能的预防和/或治疗选择,需要进一步研究。抗炎药物很常见,每种药物可能表现出不同的抗肿瘤作用。因此,本研究在体外和体内研究了不同的子宫颈癌抗炎模型。在子宫颈癌HeLa、VIPA、INBL和SiHa细胞系中测试了塞来昔布、舒林酸、尼美舒利、地塞米松、甲氯芬那酸、氟芬那酸和甲芬那酸。评估了这些药物的细胞毒性。塞来昔布、舒林酸、尼美舒利、甲芬那酸和氟芬那酸在某些细胞系中表现出轻微至中度毒性(100μM时细胞死亡10 - 40%),而甲氯芬那酸在所有测试细胞系中均表现出显著的细胞毒性(100μM时细胞死亡50 - 90%)。在子宫颈癌的小鼠模型(免疫缺陷和免疫健全)中测试了甲氯芬那酸,其表现出肿瘤生长显著减少和小鼠存活率提高。结果表明,在所评估的抗炎药物中,甲氯芬那酸细胞毒性最强,在小鼠模型中具有显著的抗肿瘤作用。后续研究有必要评估这种药物的临床效用。

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