目的 探討木犀草素對口腔鱗狀細胞癌（OSCC）惡性表型干預作用及相關機制。方法 于在線數(shù)據(jù)庫中檢索木犀草素與OSCC的交集靶點并導入R軟件開展富集分析。并由Cytoscape軟件根據(jù)交集靶點度值篩選核心靶點。經(jīng)UALCAN數(shù)據(jù)庫對核心靶點在OSCC組織中的表達進行進一步分析。通過CCK-8、Transwell、平板集落形成、劃痕與流式實驗分別測定木犀草素對細胞活性、侵襲、增殖、遷移與凋亡能力的影響；由Western blotting實驗檢測蛋白的相對表達量；最后通過裸鼠成瘤實驗觀察木犀草素對裸鼠成瘤情況、腫瘤質量及相關靶點蛋白表達的影響。結果 收集到木犀草素與OSCC交集靶點277個，前3位核心靶點為Src酪氨酸激酶（SRC）、磷脂酰肌醇-3激酶調節(jié)亞單位1（PIK3R1）與蛋白激酶B（AKT1）。相比正常組織，OSCC組織內SRC、PIK3R1與AKT1的mRNA高表達（P＜0.05）。京都基因與基因組百科全書（KEGG）富集分析結果顯示，交集基因于信號通路PI3K/Akt上富集。相較于對照組，木犀草素組細胞的細胞活性、增殖、遷移和侵襲能力受抑，凋亡能力提高，且具有藥物濃度相關性（P＜0.05）。相較于對照組，木犀草素組SRC、PIK3R1、p-PI3K、p-Akt蛋白表達隨藥物濃度呈相關性降低（P＜0.05）。木犀草素對裸鼠成瘤、腫瘤質量大小具有抑制作用。同時，與對照組比較，木犀草素組瘤體的SRC、PIK3R1、p-PI3K、p-Akt蛋白表達降低（P＜0.05）。結論 木犀草素可降低SRC與PIK3R1蛋白表達，同時下調PI3K/Akt軸使OSCC細胞侵襲、遷移與增殖能力受抑，促進細胞凋亡。

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

山東省醫(yī)藥衛(wèi)生科技項目（ 202308020503）；濰坊市科技發(fā)展計劃項目（2022YX047）