拓扑异构酶 IIα (TOP2A) 是一种参与 DNA 复制、转录、重组和染色质重塑的酶，存在于多种癌症中。然而，TOP2A 调节在口腔癌进展中的作用尚未得到充分解释。我们研究了 TOP2A 抑制对口腔癌细胞中细胞存活、代谢和癌症干细胞自我更新功能的影响。口腔癌细胞系 SCC25 在完全 DMEM/F12 培养基中培养，并用 5μM 依托泊苷（拓扑异构酶 II 抑制剂）处理48小时。使用 Seahorse 测定评估细胞代谢的关键参数，包括细胞外酸化率 (ECAR) 和基于癌细胞耗氧率的线粒体氧化磷酸化。进行蛋白质印迹以评估对照和依托泊苷处理组制备的细胞裂解物中与增殖相关的蛋白质（生存素、IL-6）和癌症干细胞功能（Oct4、Sox2）。采用单因素方差分析结合Dunnett多重比较检验进行统计分析。依托泊苷显着抑制TOP2A蛋白表达（P<0.05）。此外，TOP2A 抑制降低了线粒体呼吸参数，包括基础呼吸、最大呼吸和 ATP 产生。然而，TOP2A 抑制对糖酵解功能没有影响。此外，抑制TOP2A后，增殖标志物survivin和IL-6显着降低（P<0.05）。相反，癌症干细胞标志物 Oct-4 和 Sox 2 的蛋白表达没有改变。这些结果表明，通过减少线粒体代谢重编程，从而下调关键的抗凋亡和促生存介质，抑制 TOP2A 更有效。因此，TOP2A代表了一个理想的治疗靶点，并为OSCC提供了潜在的治疗策略。

Topoisomerase IIα (TOP2A), is an enzyme involved in DNA replication, transcription, recombination, and chromatin remodeling and is found in a variety of cancers. However, the role of TOP2A regulation in oral cancer progression is not fully explained. We investigated the effect of TOP2A inhibition on cell survival, metabolism, and cancer stem cell self-renewal function in oral cancer cells.Oral carcinoma cell line SCC25 was cultured in complete DMEM/F12 media and treated with 5μM of Etoposide (Topoisomerase II inhibitor) for 48h. The critical parameters of cellular metabolism, including extracellular acidification rate (ECAR) and mitochondrial oxidative phosphorylation based on the oxygen consumption rate of cancer cells were assessed using Seahorse assay. Western blotting was performed to assess the proteins that are associated with proliferation (Survivin, IL-6) and cancer stem cell function (Oct4, Sox2) in cell lysates prepared from control and etoposide treated groups. Statistical analysis was performed using One-way ANOVA with Dunnett's multiple comparisons test.The protein expression of TOP2A was significantly (P<0.05) inhibited by etoposide. Additionally, TOP2A inhibition decreased the mitochondrial respiratory parameters including basal respiration, maximal respiration and ATP production. However, TOP2A inhibition has no impact on glycolytic function. Moreover, the proliferative marker survivin and IL-6 showed a significant (P<0.05) decrease after TOP2A inhibition. Conversely, the protein expression of cancer stem cell markers Oct-4 and Sox 2 were not altered.These results indicate that inhibition of TOP2A is more efficacious by decreasing the mitochondrial metabolic reprogramming and thereby downregulating the key anti-apoptotic and pro-survival mediators. Thus, TOP2A represents an ideal therapeutic target and offers a potential treatment strategy for OSCC.