Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou, China.
Department of Toxicology, College of Public Health, Zhengzhou University, Zhengzhou, China.
Toxicol Appl Pharmacol. 2024 Apr;485:116916. doi: 10.1016/j.taap.2024.116916. Epub 2024 Mar 26.
This study aims to explore the impact and underlying mechanism of sulforaphane (SFN) intervention on the migration and invasion of lung adenocarcinoma induced by 7, 8-dihydroxy-9, 10-epoxy-benzo (a) pyrene (BPDE). Human lung adenocarcinoma A549 cells were exposed to varying concentrations of BPDE (0.25, 0.50, and 1.00 μM) and subsequently treated with 5 μM SFN. Cell viability was determined using CCK8 assay, while migration and invasion were assessed using Transwell assays. Lentivirus transfection was employed to establish NLRP12 overexpressing A549 cells. ELISA was utilized to quantify IL-33, CXCL12, and CXCL13 levels in the supernatant, while quantitative real-time PCR (qRT-PCR) and Western Blot were used to analyze the expression of NLRP12 and key factors associated with canonical and non-canonical NF-κB pathways. Results indicated an increase in migratory and invasive capabilities, concurrent with heightened expression of IL-33, CXCL12, CXCL13, and factors associated with both canonical and non-canonical NF-κB pathways. Moreover, mRNA and protein levels of NLRP12 were decreased in BPDE-stimulated A549 cells. Subsequent SFN intervention attenuated BPDE-induced migration and invasion of A549 cells. Lentivirus-mediated NLRP12 overexpression not only reversed the observed phenotype in BPDE-induced cells but also led to a reduction in the expression of critical factors associated with both canonical and non-canonical NF-κB pathways. Collectively, we found that SFN could inhibit BPDE-induced migration and invasion of A549 cells by upregulating NLRP12, thereby influencing both canonical and non-canonical NF-κB pathways.
这项研究旨在探讨萝卜硫素（SFN）干预对 7,8-二羟-9,10-环氧苯并（a）芘（BPDE）诱导的肺腺癌细胞迁移和侵袭的影响及其潜在机制。将人肺腺癌细胞 A549 暴露于不同浓度的 BPDE（0.25、0.50 和 1.00 μM）中，然后用 5 μM SFN 处理。用 CCK8 测定细胞活力，用 Transwell 测定迁移和侵袭。采用慢病毒转染建立 NLRP12 过表达 A549 细胞。ELISA 用于测定上清液中 IL-33、CXCL12 和 CXCL13 的水平，定量实时 PCR（qRT-PCR）和 Western Blot 用于分析 NLRP12 及其与经典和非经典 NF-κB 通路相关的关键因子的表达。结果表明，迁移和侵袭能力增强，同时 IL-33、CXCL12、CXCL13 和与经典和非经典 NF-κB 通路相关的因子表达升高。此外，BPDE 刺激的 A549 细胞中 NLRP12 的 mRNA 和蛋白水平降低。随后的 SFN 干预减弱了 BPDE 诱导的 A549 细胞迁移和侵袭。慢病毒介导的 NLRP12 过表达不仅逆转了 BPDE 诱导细胞的表型，而且还导致与经典和非经典 NF-κB 通路相关的关键因子的表达减少。综上所述，我们发现 SFN 可以通过上调 NLRP12 抑制 BPDE 诱导的 A549 细胞迁移和侵袭，从而影响经典和非经典 NF-κB 通路。
