Department of Bacteriology, Osaka Dental University, 8-1, Kuzuha-Hanazono, Hirakata, Osaka 573-1121, Japan.
Department of Bacteriology, Osaka Dental University, 8-1, Kuzuha-Hanazono, Hirakata, Osaka 573-1121, Japan.
Arch Oral Biol. 2024 Apr;160:105897. doi: 10.1016/j.archoralbio.2024.105897. Epub 2024 Jan 22.
Resveratrol is a natural phytoalexin that has anti-inflammatory properties, reverses doxorubicin resistance, and inhibits epithelial-mesenchymal transition (EMT) in many types of cancer cells. Fusobacterium nucleatum is reportedly enriched in oral squamous cell carcinoma (OSCC) tissues compared to adjacent normal tissues, sparking interest in the relationship between F. nucleatum and OSCC. Recently, F. nucleatum was shown to be associated with EMT in OSCC. In the present study, we aimed to investigate the effects of the natural plant compound resveratrol on F. nucleatum-induced EMT in OSCC.
F. nucleatum was co-cultured with OSCC cells, with a multiplicity of infection (MOI) of 300:1. Resveratrol was used at a concentration of 10 μM. Cell Counting Kit-8 and wound healing assays were performed to examine the viability and migratory ability of OSCC cells. Subsequently, real-time RT-PCR was performed to investigate the gene expression of EMT-related markers. Western blotting and immunofluorescence analyses were used to further analyze the expression of the epithelial marker E-cadherin and the EMT transcription factor SNAI1.
Co-cultivation with F. nucleatum did not significantly enhance cell viability. The co-cultured cells displayed similarities to the positive control of EMT, exhibiting enhanced migration and expression changes in EMT-related markers. SNAI1 was significantly upregulated, whereas E-cadherin, was significantly downregulated. Notably, resveratrol inhibited F. nucleatum-induced cell migration, decreasing the expression of SNAI1.
Resveratrol inhibited F. nucleatum-induced EMT by downregulating SNAI1, which may provide a target for OSCC treatment.
白藜芦醇是一种天然植物抗毒素,具有抗炎特性,可逆转多柔比星耐药性,并抑制多种癌细胞的上皮-间充质转化(EMT)。据报道,相比于相邻的正常组织,具核梭杆菌在口腔鳞状细胞癌(OSCC)组织中更为丰富,这引发了人们对具核梭杆菌与 OSCC 之间关系的兴趣。最近,研究表明,具核梭杆菌与 OSCC 中的 EMT 有关。在本研究中,我们旨在研究天然植物化合物白藜芦醇对 OSCC 中具核梭杆菌诱导的 EMT 的影响。
将具核梭杆菌与 OSCC 细胞以感染复数(MOI)为 300:1 进行共培养。白藜芦醇的使用浓度为 10 μM。通过细胞计数试剂盒-8 和划痕愈合实验检测 OSCC 细胞的活力和迁移能力。随后,通过实时 RT-PCR 检测 EMT 相关标志物的基因表达。通过 Western blot 和免疫荧光分析进一步分析上皮标志物 E-钙黏蛋白和 EMT 转录因子 SNAI1 的表达。
与具核梭杆菌共培养并未显著增强细胞活力。共培养的细胞与 EMT 的阳性对照相似,表现出增强的迁移能力和 EMT 相关标志物的表达变化。SNAI1 显著上调,而 E-钙黏蛋白显著下调。值得注意的是,白藜芦醇抑制了具核梭杆菌诱导的细胞迁移,降低了 SNAI1 的表达。
白藜芦醇通过下调 SNAI1 抑制了具核梭杆菌诱导的 EMT,这可能为 OSCC 的治疗提供了一个靶点。