Glyburide Attenuates B(a)p and LPS-Induced Inflammation-Related Lung Tumorigenesis in Mice

Abstract Background: Glyburide (Gly) serves as inhibitor of NLRP3 inflammasome, which is also one of the most common medication used in the treatment of type 2 diabetes. Although accumulating evidences suggest that Gly could affect cancer risk and tumor growth, the role of chronic Gly treatment in lung tumorigenesis remains unclear. In this study, we evaluated whether Gly inhibited the occurrence of lung cancer and explored the possible mechanisms in the non-diabetes mice model of inflammation-related lung cancer induced by benzo(a)pyrene [B(a)p] plus lipopolysaccharide (LPS).Methods: The C57BL/6J mice exposed to B(a)p (1mg/mouse, once a week for 4 times) and 3 weeks later instilled intratracheally with LPS (2.5μg/mouse, once every three weeks for 5 times), and the Gly was administered by gavage (at a dose of 10μl/g body weight) one week before the mice exposed to B(a)p until the animal model finished (the week of the first time of Gly treatment named Week 0). At 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.Results: Vehicles and tricaprylin+Gly could not induce lung tumorigenesis in the whole process. The incidence and the mean tumor count of mice in B(a)P/LPS+Gly group was decreased compared to those in B(a)p plus LPS group respectively. Histopathological examination found that Gly-treatment alleviated inflammatory changes compared with mice exposed to B(a)p plus LPS and revealed a reduction of the number of pathological tumor nest in the B(a)P/LPS+Gly group compared to the B(a)p plus LPS group. The expression of NLRP3, IL-1β and Cleaved-IL-1β protein was significantly increased in B(a)p plus LPS group compared to Vehicle control group, but decreased in B(a)P/LPS+Gly(0.96mg/kg) group compared to B(a)p plus LPS group.Conclusions: Glyburide might inhibit NLRP3 inflammasome to attenuate B(a)p plus LPS-induced inflammation-related lung tumorigenesis in non-diabetes mice.