BACKGROUND Head and neck squamous cell carcinoma (HNSCC) is one of the most common lethal tumors with a high recurrence rate and low survival rate. Therefore, an urgent need exists for novel and effective treatment strategies for HNSCC patients. METHODS Osthole, a natural ingredient extracted from Cnidium monnieri (L.) 'Cusson', has multiple pharmacological effects including antineoplastic activity. Regrettably, the antineoplastic effect of osthole in HNSCC cells remains undefined. We utilize in vitro assays to assess the anti-proliferative effects of osthole in HNSCC cells and tumorigenesis assays using FaDu cells in murine HNSCC models to assess in vivo function. Moreover, the possible molecular mechanisms of Osthole on HNSCC cells was also investigated. RESULTS Our findings show that the anti-proliferation effect of osthole might function through induction of cell cycle arrest (G2/M phase) and apoptosis in HNSCC. Osthole could also down-regulating the protein level of cell cycle and apoptosis related proteins, such as Bcl-2, PARP1, Survivin, CyclinB1 and Cdc2, while up-regulating expression of Cleaved Caspase3/9, Cleaved PARP1 and Bax. Similarly, osthole suppressed the in vivo growth of FaDu cells in a subcutaneous tumor model. In terms of mechanism, our data show that osthole can suppress the PI3K/AKT pathway. CONCLUSIONS In the current study, our in vitro and in vivo assay showed the suppressive effect of Osthole on HNSCC cells through induce cell cycle arrest (G2/M phase) and apoptosis. Moreover, the action mechanisms of Osthole on proliferation related signaling pathways was disclosed. Our present study suggests that osthole might be used as an effective therapeutic agent for patients with HNSCC.

中文翻译：

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Osthole通过抑制PI3K / AKT信号传导通路诱导头颈部鳞状细胞癌的细胞周期停滞和凋亡。

背景技术头颈鳞状细胞癌（HNSCC）是复发率高，存活率低的最常见的致死性肿瘤之一。因此，迫切需要针对HNSCC患者的新颖有效的治疗策略。方法Osthole是从Cnidium monnieri（L.）'Cusson'提取的天然成分，具有多种药理作用，包括抗肿瘤活性。遗憾的是，在HNSCC细胞中，蛇床子素的抗肿瘤作用仍未确定。我们利用体外测定法评估osthole在HNSCC细胞中的抗增殖作用，并利用FaDu细胞在鼠类HNSCC模型中进行肿瘤发生测定以评估体内功能。此外，还研究了Osthole对HNSCC细胞的可能的分子机制。结果我们的研究结果表明，osthole的抗增殖作用可能是通过诱导HNSCC细胞周期停滞（G2 / M期）和凋亡而发挥作用。Osthole还可以下调细胞周期蛋白和凋亡相关蛋白（例如Bcl-2，PARP1，Survivin，CyclinB1和Cdc2）的蛋白水平，同时上调Cleaved Caspase3 / 9，Cleaved PARP1和Bax的表达。同样，在皮下肿瘤模型中，osthole抑制了FaDu细胞的体内生长。就机理而言，我们的数据表明，蛇床子素可以抑制PI3K / AKT途径。结论在当前的研究中，我们的体外和体内试验显示了Osthole通过诱导细胞周期停滞（G2 / M期）和细胞凋亡对HNSCC细胞的抑制作用。此外，公开了Osthole对增殖相关的信号传导途径的作用机理。