Notch信号通路影响多种器官的发育和功能，且与肿瘤的发生发展密切相关。不同肿瘤Notch信号通路作用也不同。舌癌是常见的头颈部恶性肿瘤，Notch通路在舌癌中的功能及分子机制目前尚不清楚。本课题组前期预实验发现Notch信号在舌癌中可能起到癌基因的作用。本研究拟在此基础上，利用临床样本及细胞学实验等，阐明Notch信号通路在舌癌发生发展中的作用及其可能的分子机制，建立裸鼠舌癌种植瘤模型，观察多种Notch信号抑制剂对舌癌增殖及转移能力的抑制作用，及其治疗舌癌的疗效及毒性，为Notch信号通路抑制剂治疗舌癌的临床应用奠定实验基础。

The Notch signaling pathway is highly conserved and regulates cell-fate decisions throughout embryonic development and adult life, and play an important role in tumor occurrence and development. But numerous studies have reported both the tumor-suppressive and oncogenic roles of the Notch pathway, indicating that Notch activity regulates tumor biology in a complex, context-dependent manner. Tongue cancer is the most common head and neck cancer, but the roles of Notch signaling pathway in the carcinogenesis and progress of tongue are still conflicted. Our preliminary data showed the oncogenic roles of Notch pathway in tongue cancer. The aim of this project is to investigate the roles and underlying molecular mechanism of Notch signaling pathway in tongue cancer. And the experimental therapy of tongue cancer with inhibitors of Notch signaling pathway was designed using nude mice transplantable tumors model. The results of the present project will provide valuable preclinical data for the clinical application of Notch signaling pathway as novel therapy targets for tongue cancer.

Notch信号通路与肿瘤的发生发展密切相关，不同肿瘤中Notch信号通路作用不同。舌癌作为头颈部癌症中较常见的恶性肿瘤之一，Notch信号通路在舌癌中的功能及分子机制目前尚不清楚。本课题的目的是探寻Notch信号通路在舌癌中的作用并寻找治疗舌癌的新方法。首先我们利用免疫组化法比较了人舌癌组织和癌旁组织中的Notch信号通路的表达情况。接着我们利用体内外实验，观察舌癌细胞的Notch信号通路受抑制或过表达后，舌癌细胞增殖、迁移、侵袭和凋亡情况的改变。另一方面，我们筛选出对舌癌细胞株有效的Notch信号通路抑制剂，将该抑制剂作用于舌癌细胞株后观察细胞株增殖、凋亡能力改变，同时在裸鼠荷瘤模型上观察抑制剂疗效及毒性。通过上述实验，我们发现Notch1、Notch2在舌癌组织中的表达量明显高于癌旁组织；Notch1、Notch2在舌癌细胞中表达下调后，体内外实验中舌癌细胞的增殖、迁移、侵袭能力下降，凋亡能力增加；反之当Notch1、Notch2在舌癌细胞中过表达后，均得到相反结果；而运用有效的Notch信号通路抑制剂作用于舌癌细胞能够很好的抑制舌癌细胞的增殖能力，促进细胞凋亡。通过以上结果我们可知，Notch信号通路在舌癌中起着促癌基因的作用。