摘要
慢性炎症在与香烟烟雾有关的致癌性中起着至关重要的作用。因此,抗炎药物,如非类固醇类抗炎药物(NSAIDs),为癌症的化学预防提供了合理的策略。我们检测塞来昔布(一种选择性环氧合酶-2(COX-2)抑制剂)和利克飞龙(COX-1、COX-2、5 -脂氧合酶(5-LOX)抑制剂)调节新生小鼠的癌变的能力,新生小鼠先暴露于香烟主流烟雾(MCS)中4个月,然后在过滤后的空气中三个半月。在初步毒性研究和化学预防研究中使用瑞士591H小鼠。暴露于MCS造成小鼠肺气肿、肺泡和支气管上皮增生、血管增生、微腺瘤、腺瘤、恶性肿瘤以及肾小管和膀胱乳头状上皮增生。塞来昔布(1600毫克/公斤饲喂)和更好的利克飞龙(960毫克/公斤饲喂)按照模仿对当前吸烟者干预的方案对小鼠给药,能显著降低MCS诱导的炎症性质的改变,包括肺气肿、肺泡上皮增生及微腺瘤和尿道增生性病变。此外,塞来昔布抑制肺腺瘤的产生量,NSAIDs 显示了在降低肺癌发展方面的某些作用。甚至在停止暴露于MCS后按照方案继续给药,塞来昔布表现出了一些保护作用。然而,对暴露于MCS的小鼠长期给药时,所有药物尤其是塞来昔布表现出肝毒性,影响生存能力和体重。
关键词: 塞来昔布,化学预防,香烟烟雾,利克飞龙,肺肿瘤。
图形摘要
Current Cancer Drug Targets
Title:Modulation by Licofelone and Celecoxib of Experimentally Induced Cancer and Preneoplastic Lesions in Mice Exposed to Cigarette Smoke
Volume: 15 Issue: 3
关键词: 塞来昔布,化学预防,香烟烟雾,利克飞龙,肺肿瘤。
摘要: Chronic inflammation plays a crucial role in cigarette smoke-related carcinogenesis. Accordingly, anti-inflammatory agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), provide a rational strategy in cancer chemoprevention. We assayed celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, and licofelone, an inhibitor of COX-1, COX-2, and 5- lipoxygenase (5-LOX), for the ability to modulate carcinogenesis in neonatal mice exposed to mainstream cigarette smoke (MCS) for 4 months and thereafter kept in filtered air for 3.5 months. A preliminary toxicity study and a chemoprevention study involved the use of 591 Swiss H mice. Exposure to MCS caused a variety of pulmonary emphysema, alveolar and bronchial epithelial hyperplasias, proliferation of blood vessels, microadenomas, adenomas and malignant tumors, as well as kidney tubular and urinary bladder papillary epithelial hyperplasias. Celecoxib (1600 mg/kg diet) and even better licofelone (960 mg/kg diet) were able to significantly attenuate the MCS-induced alterations of inflammatory nature, including pulmonary emphysema, alveolar epithelial hyperplasias and microadenomas and urinary tract hyperplastic lesions when given to mice according to a protocol that mimics an intervention in current smokers. Moreover, celecoxib attenuated the yield of lung adenomas and both NSAIDs showed some involvement in lowering the progression to cancer in the lung. Celecoxib exhibited some protective effects even when given according to a protocol involving its administration after discontinuation of exposure to MCS. However, both agents and especially celecoxib showed some hepatotoxicity and affected survival and body weight gain of mice when administered to MCS-exposed mice in the long term.
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Cite this article as:
Modulation by Licofelone and Celecoxib of Experimentally Induced Cancer and Preneoplastic Lesions in Mice Exposed to Cigarette Smoke, Current Cancer Drug Targets 2015; 15 (3) . https://dx.doi.org/10.2174/1568009615666150216170008
DOI https://dx.doi.org/10.2174/1568009615666150216170008 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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