Huo Jiaying, Qi Jianhua, Ren Qixuan
Hebei Medical University, Shijiazhuang, Hebei, China.
Handan Stomatological Hospital, Handan, Hebei, China.
Integr Cancer Ther. 2025 Jan-Dec;24:15347354251375464. doi: 10.1177/15347354251375464. Epub 2025 Sep 16.
Oral squamous cell carcinoma (OSCC) is an invasive cancer with a high rate of metastasis and recurrence. Anthraquinone natural active element sennoside A (SA) has demonstrated a repressive effect on several malignancies. Its impact on OSCC is still unknown, though.
The toxicity effect of SA on OSCC cells was examined by CCK8, to screen the appropriate concentrations for following assays. The effect of SA on proliferation, ferroptosis and immune evasion of OSCC was assessed by CCK-8, DCHF-DA staining, biochemical detection, ELISA, and western blotting. The mechanism of SA on OSCC was determined by western blotting and immunofluorescence. Besides, in vivo effect of SA was investigated on tumor-bearing mice using HE staining, immunohistochemistry, and western blotting.
SA reduced SCC7 and CAL27 cell viability, with a IC50 values of 94.38 and 77.41 μM, respectively. SA downregulated the expressions of GPX4 and xCT expression and the SOD level, but elevated the levels of ROS, MDA, and Fe in SCC7 and CAL27 cells. SA decreased the PD-L1 expression, whereas increased the cytotoxicity of CD8 T cells and the concentrations of IFN-γ, IL-2, and TNF-α of SCC7 and CAL27 cells. Mechanically, SA reduced the phosphorylation of NF-κB and IκBα in SCC7 and CAL27 cells. Also, RANKL treatment reversed the outcomes of indicators involved in proliferation, ferroptosis and immune evasion in SCC7 cells. In vivo, SA reduced tumor weight and size, the expression levels of GPX4 and PD-L1 and the phosphorylation of NF-κB and IκBα, but enhanced the IFN-γ level in mice xenografted with SCC7 cells.
SA suppressed proliferation and immune evasion, but induced ferroptosis through the inactivation of NF-κB pathway in OSCC.
口腔鳞状细胞癌（OSCC）是一种具有高转移率和复发率的侵袭性癌症。蒽醌类天然活性成分番泻苷A（SA）已显示出对多种恶性肿瘤具有抑制作用。然而，其对OSCC的影响尚不清楚。
通过CCK8检测SA对OSCC细胞的毒性作用，以筛选后续实验的合适浓度。通过CCK-8、DCHF-DA染色、生化检测、ELISA和蛋白质印迹法评估SA对OSCC增殖、铁死亡和免疫逃逸的影响。通过蛋白质印迹法和免疫荧光法确定SA对OSCC的作用机制。此外，使用苏木精-伊红染色、免疫组织化学和蛋白质印迹法研究SA对荷瘤小鼠的体内作用。
SA降低了SCC7和CAL27细胞活力，IC50值分别为94.38和77.41 μM。SA下调了SCC7和CAL27细胞中GPX4和xCT的表达以及SOD水平，但提高了ROS、MDA和Fe的水平。SA降低了PD-L1表达，而增加了CD8 T细胞的细胞毒性以及SCC7和CAL27细胞中IFN-γ、IL-2和TNF-α的浓度。机制上，SA降低了SCC7和CAL27细胞中NF-κB和IκBα的磷酸化水平。此外，RANKL处理逆转了SCC7细胞中增殖、铁死亡和免疫逃逸相关指标的结果。在体内，SA降低了接种SCC7细胞的小鼠的肿瘤重量和大小、GPX4和PD-L1的表达水平以及NF-κB和IκBα的磷酸化水平，但提高了IFN-γ水平。
SA通过使OSCC中NF-κB通路失活来抑制增殖和免疫逃逸，但诱导铁死亡。
