Abstract：
Notch signaling is associated with many human malignancies, including oral squamous cell carcinoma (OSCC). However, the exact function of Notch signaling in OSCC remains unclear. Here, we investigated the effect of Notch signaling inhibition using a γ-secretase inhibitor (DAPT) on OSCC behaviours in vitro. Bioinformatic analysis of public-available gene expression profiles revealed the dysregulation of the Notch signaling pathway in OSCC compared with normal tissues, indicating the role of Notch signaling in OSCC regulation. RNA sequencing analysis of DAPT-treated human OSCC cells revealed the dysregulation of genes related to cell cycle-related pathways. Blocking Notch signaling significantly inhibited cell proliferation. DAPT-induced G0/G1 cell cycle arrest induced cell apoptosis. Furthermore, cell migration and invasion were also reduced in DAPT-treated cells. These findings indicate that Notch signaling activation participates in OSCC regulation by promoting cell growth, cell cycle progression, cell migration, and invasion. These mechanisms could facilitate OSCC progression. These results imply the potential use of Notch signaling inhibitors as a candidate adjuvant treatment in OSCC patients.
摘要：
Notch信号与许多人类恶性肿瘤有关，包括口腔鳞状细胞癌（OSCC）。然而,Notch信号在OSCC中的确切功能尚不清楚.这里,我们研究了使用γ-分泌酶抑制剂（DAPT）抑制Notch信号对体外OSCC行为的影响。公开可用的基因表达谱的生物信息学分析揭示了与正常组织相比，OSCC中Notch信号通路的失调。说明Notch信号在OSCC调控中的作用。DAPT处理的人OSCC细胞的RNA测序分析揭示了与细胞周期相关途径相关的基因的失调。阻断Notch信号显著抑制细胞增殖。DAPT诱导G0/G1细胞周期阻滞诱导细胞凋亡。此外，在DAPT处理的细胞中,细胞迁移和侵袭也减少.这些发现表明Notch信号激活通过促进细胞生长参与OSCC调控,细胞周期进程，细胞迁移，和入侵。这些机制可以促进OSCC进展。这些结果暗示Notch信号传导抑制剂作为OSCC患者的候选辅助治疗的潜在用途。
