Glyburide (Gly) could inhibit NLRP3 inflammasome, as well as could be treated with Type 2 diabetes as a common medication. Despite more and more studies show that Gly could influence cancer risk and tumor growth, it remains unclear about the effect of Gly in lung tumorigenesis. To evaluate whether Gly inhibited lung tumorigenesis and explore the possible mechanisms, a benzo(a)pyrene [B(a)p] plus lipopolysaccharide (LPS)-induced non-diabetes mice model was established with B(a)p for 4 weeks and once a week (1 mg/mouse), then instilled with LPS for 15 weeks and once every 3 weeks (2.5 μg/mouse) intratracheally. Subsequently, Gly was administered by gavage (10 μl/g body weight) 1 week before B(a)p were given to the mice until the animal model finished (when Gly was first given named Week 0). At the end of the experiment called Week 34, we analyzed the incidence, number and histopathology of lung tumors, and detected the expression of NLRP3, IL-1β, and Cleaved-IL-1β protein. We found that vehicles and tricaprylin+Gly could not cause lung carcinogenesis in the whole process. While the incidence and mean tumor count of mice in B(a)P/LPS+Gly group were decreased compared with B(a)p/LPS group. Moreover, Gly could alleviate inflammatory changes and reduce pathological tumor nest numbers compared with mice administrated with B(a)p/LPS in histopathological examination. The B(a)p/LPS increased the expression of NLRP3, IL-1β, and Cleaved-IL-1β protein significantly than Vehicle, whereas decreased in B(a)P/LPS+Gly (0.96 mg/kg) group compared with B(a)p/LPS group. Results suggested glyburide might inhibit NLRP3 inflammasome to attenuate inflammation-related lung tumorigenesis caused by intratracheal instillation of B(a)p/LPS in non-diabetes mice.

中文翻译：

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格列本脲减弱 B(a)p 和 LPS 诱导的小鼠炎症相关肺肿瘤发生

格列本脲 (Gly) 可以抑制 NLRP3 炎症小体，并且可以作为一种常用药物治疗 2 型糖尿病。尽管越来越多的研究表明 Gly 可以影响癌症风险和肿瘤生长，但 Gly 在肺肿瘤发生中的作用仍不清楚。为了评估甘氨酸是否抑制肺肿瘤发生并探索可能的机制，使用 B(a)p 建立苯并 (a) 芘 [B(a)p] 加脂多糖 (LPS) 诱导的非糖尿病小鼠模型 4 周，然后每周一次（1 毫克/小鼠），然后气管内灌注 LPS 15 周，每 3 周一次（2.5 微克/小鼠）。随后，在给予小鼠 B(a)p 前 1 周通过管饲法（10 μl/g 体重）给予 Gly，直到动物模型完成（当 Gly 首次给予时，命名为第 0 周）。在称为第 34 周的实验结束时，我们分析了肺肿瘤的发病率、数量和组织病理学，并检测了 NLRP3、IL-1β 和 Cleaved-IL-1β 蛋白的表达。我们发现在整个过程中，载体和三辛酸+甘氨酸都不会引起肺癌的发生。而与B(a)p/LPS组相比，B(a)P/LPS+Gly组小鼠的发病率和平均肿瘤计数降低。此外，与在组织病理学检查中使用 B(a)p/LPS 的小鼠相比，Gly 可以减轻炎症变化并减少病理性肿瘤巢数。B(a)p/LPS 比 Vehicle 显着增加 NLRP3、IL-1β 和 Cleaved-IL-1β 蛋白的表达，而 B(a)P/LPS+Gly (0.96 mg/kg) 组与B(a)p/LPS 组。