目的 探讨木犀草素对口腔鳞状细胞癌（OSCC）恶性表型干预作用及相关机制。方法 于在线数据库中检索木犀草素与OSCC的交集靶点并导入R软件开展富集分析。并由Cytoscape软件根据交集靶点度值筛选核心靶点。经UALCAN数据库对核心靶点在OSCC组织中的表达进行进一步分析。通过CCK-8、Transwell、平板集落形成、划痕与流式实验分别测定木犀草素对细胞活性、侵袭、增殖、迁移与凋亡能力的影响；由Western blotting实验检测蛋白的相对表达量；最后通过裸鼠成瘤实验观察木犀草素对裸鼠成瘤情况、肿瘤质量及相关靶点蛋白表达的影响。结果 收集到木犀草素与OSCC交集靶点277个，前3位核心靶点为Src酪氨酸激酶（SRC）、磷脂酰肌醇-3激酶调节亚单位1（PIK3R1）与蛋白激酶B（AKT1）。相比正常组织，OSCC组织内SRC、PIK3R1与AKT1的mRNA高表达（P＜0.05）。京都基因与基因组百科全书（KEGG）富集分析结果显示，交集基因于信号通路PI3K/Akt上富集。相较于对照组，木犀草素组细胞的细胞活性、增殖、迁移和侵袭能力受抑，凋亡能力提高，且具有药物浓度相关性（P＜0.05）。相较于对照组，木犀草素组SRC、PIK3R1、p-PI3K、p-Akt蛋白表达随药物浓度呈相关性降低（P＜0.05）。木犀草素对裸鼠成瘤、肿瘤质量大小具有抑制作用。同时，与对照组比较，木犀草素组瘤体的SRC、PIK3R1、p-PI3K、p-Akt蛋白表达降低（P＜0.05）。结论 木犀草素可降低SRC与PIK3R1蛋白表达，同时下调PI3K/Akt轴使OSCC细胞侵袭、迁移与增殖能力受抑，促进细胞凋亡。

Objective To investigate the effect and mechanism of luteolin on the malignant phenotype of oral squamous cell carcinoma (OSCC). Methods The intersection targets of luteolin and OSCC were searched in the online database and imported into R software for enrichment analysis. The core targets were screened by Cytoscape software according to the degree value of intersection targets. The expression of core targets in OSCC tissues was further analyzed by UALCAN database. The effects of luteolineolin on cell viability, invasion, proliferation, migration and apoptosis were determined by CCK-8, Transwell, plate colony formation, scratch and flow cytometry. The relative protein expression was detected by Western blotting. The effect of luteolin on tumor formation, tumor weight and the expression of related target proteins in nude mice were observed. Results A total of 277 intersection targets between luteolin and OSCC were collected, and the top three core targets were SRC, PIK3R1, and AKT1. Compared with normal tissues, the mRNA expressions of SRC, PIK3R1 and AKT1 in OSCC tissues were higher (P <0.05). KEGG enrichment analysis indicated crossgene enrichment in the PI3K/Akt signaling pathway. Compared with the control group, the cell activity, proliferation, migration and invasion ability of the luteolin group were inhibited, and the apoptosis ability was increased (P <0.05). The luteolin group had significantly lower protein expression levels of SRC, PIK3R1, p-PI3K, and p-Akt than the control group (P <0.05). Luteolin inhibited tumor formation and tumor weight in nude mice (P <0.05). Meanwhile, the protein expression of SRC, PIK3R1, p-PI3K and p-Akt in luteolin group was lower than that in control group (P <0.05). Conclusion Luteolin reduces the expression of SRC and PIK3R1 proteins, weakens the PI3K/Akt signaling pathway, and then inhibits the invasion, migration and proliferation of OSCC cells, and induces cell apoptosis.

R285.5

山东省医药卫生科技项目（ 202308020503）；潍坊市科技发展计划项目（2022YX047）