Huang Wei, Wang Chenyang, Zhang Hui
Department of Hepatobiliary and Pancreatic Surgery, Third Xiangya Hospital, Central South University, Changsha, 410013 Hunan, China.
Heliyon. 2024 Jan 20;10(3):e24401. doi: 10.1016/j.heliyon.2024.e24401. eCollection 2024 Feb 15.
NLRP3 involves in the development of hepatocellular carcinoma (HCC). Eriodictyol has shown its inhibitory effect on HCC cell proliferation. However, the underlying mechanism of eriodictyol in HCC is still unclear. This study aimed to explore the effect of and mechanism of eriodictyol on HCC. In this study, compared with eriodictyol (0 μM) group, eriodictyol significantly suppressed HepG2 cells (eriodictyol of 25, 50 and 100 μM) and Huh-7 cells (eriodictyol of 50 and 100 μM) viability, invasion, tube formation, metastasis-related genes MMP3, MMP16 and angiogenesis regulator VEGFA expressions with IC of 45.63 μM and 78.26 μM , respectively. Besides, eriodictyol significantly repressed NLRP3 expression, and reduced the protein levels of NLRP3 inflammasome-related proteins, adapter protein ASC, caspase-1, interleukin (IL)-18, and IL-1β in HepG2 (eriodictyol of 25, 50 and 100 μM) and Huh-7 cells (eriodictyol of 50 and 100 μM), respectively. Meanwhile, compared with control group, NLRP3 overexpression reversed the anti-metastatic effects of 100 μM eriodictyol on HCC cells invasion, tube formation, and metastasis-related genes MMP3, MMP16 and angiogenesis regulator VEGFA expressions, whereas NLRP3 knockdown enhanced the anti-metastatic effects of 100 μM eriodictyol on HCC cells. , compared with control group, eriodictyol significantly reduced the tumor growth, liver damage, inhibited the activation of NLRP3 inflammasome, and improved liver function, whereas NLRP3 overexpressing neutralized the anti-tumor effects of eriodictyol and degraded liver function. Hence, eriodictyol inhibited HCC cell viability, motility, angiogenesis and tumor growth via NLRP3 inflammasome inactivation both and .
NLRP3参与肝细胞癌（HCC）的发展。圣草酚已显示出对HCC细胞增殖的抑制作用。然而，圣草酚在HCC中的潜在机制仍不清楚。本研究旨在探讨圣草酚对HCC的作用及机制。在本研究中，与圣草酚（0 μM）组相比，圣草酚显著抑制HepG2细胞（25、50和100 μM的圣草酚）和Huh-7细胞（50和100 μM的圣草酚）的活力、侵袭、管腔形成、转移相关基因MMP3、MMP16和血管生成调节因子VEGFA的表达，其半数抑制浓度分别为45.63 μM和78.26 μM。此外，圣草酚显著抑制NLRP3表达，并分别降低HepG2（25、50和100 μM的圣草酚）和Huh-7细胞（50和100 μM的圣草酚）中NLRP3炎性小体相关蛋白、衔接蛋白ASC、半胱天冬酶-1、白细胞介素（IL）-18和IL-1β的蛋白水平。同时，与对照组相比，NLRP3过表达逆转了100 μM圣草酚对HCC细胞侵袭、管腔形成以及转移相关基因MMP3、MMP16和血管生成调节因子VEGFA表达的抗转移作用，而NLRP3基因敲低增强了100 μM圣草酚对HCC细胞的抗转移作用。与对照组相比，圣草酚显著降低肿瘤生长、肝损伤，抑制NLRP3炎性小体的激活，并改善肝功能，而NLRP3过表达则抵消了圣草酚的抗肿瘤作用并使肝功能恶化。因此，圣草酚通过使NLRP3炎性小体失活，在体内和体外均抑制HCC细胞活力、运动能力、血管生成和肿瘤生长。
