瘦素
炎症体
癌细胞
雌激素受体
癌症研究
基因沉默
信号转导
生物
细胞生物学
化学
内分泌学
内科学
受体
癌症
乳腺癌
医学
生物化学
基因
肥胖
作者
Pawan Kumar Raut,Sang-Hyun Kim,Dong Young Choi,Gil‐Saeng Jeong,Pil-Hoon Park
标识
DOI:10.1016/j.bcp.2019.01.006
摘要
Leptin, a hormone primarily derived from adipose tissue, is known to induce tumor growth, but its underlying mechanisms of action are not clearly understood. Inflammasomes, acting as signaling platforms for controlling inflammatory responses, modulate tumor growth in a complicated manner. In this study, we investigated the role of inflammasomes in leptin-induced growth of breast cancer cells. Herein, we showed that leptin activated NLRP3 inflammasomes in MCF-7 breast cancer cells, as determined by activation of caspase-1, maturation of interleukin-1β, and increased expression of the inflammasome components, including NLRP3 and ASC. Interestingly, inhibition of the inflammasome by treatment with a pharmacological inhibitor of caspase-1 or gene silencing of NLRP3 prevented leptin-induced increase in cell viability. Moreover, suppression of apoptosis and cell cycle promotion by leptin were also significantly abolished by gene silencing of NLRP3, clearly indicating a crucial role of NLRP3 inflammasomes in leptin-induced breast cancer growth. In addition, inhibition of estrogen receptor signaling or ROS production markedly blocked leptin-induced activation of NLRP3 inflammasomes, suggesting that estrogen receptor signaling and ROS production mediate inflammasomes activation by leptin. The stimulatory effect of leptin on inflammasomes activation was also observed in MCF-7 tumor xenograft model. Furthermore, the critical roles of inflammasomes activation in leptin-induced tumor growth, suppression of apoptotic gene expression, and induction of the genes stimulating cell cycle were confirmed in a tumor xenograft model. Taken together, these results demonstrate that inflammasomes activation plays a pivotal role in leptin-induced growth of breast cancer cells via modulation of both apoptosis and cell cycle.
科研通智能强力驱动
Strongly Powered by AbleSci AI