Epigallocatechin-3-gallate (EGCG), the main active ingredient of green tea, exhibits low toxic side effect and versatile bioactivities, and its anti-cancer effect has been extensively studied. Most of the studies used cancer cell lines and xenograft models. However, whether EGCG can prevent tumor onset after cancer-associated mutations occur is still controversial. In the present study, Krt14-cre/ERT-Kras transgenic mice were developed and the expression of K-RasG12D was induced by tamoxifen. Two weeks after induction, the K-Ras mutant mice developed exophytic tumoral lesions on the lips and tongues, with significant activation of Notch signaling pathway. Administration of EGCG effectively delayed the time of appearance, decreased the size and weight of tumoral lesions, relieved heterotypic hyperplasia of tumoral lesions, and prolonged the life of the mice. The Notch signaling pathway was significantly inhibited by EGCG in the tumoral lesions. Furthermore, EGCG significantly induced cell apoptosis and inhibited the proliferation of tongue cancer cells by blocking the activation of Notch signaling pathway. Taken together, these results indicate EGCG as an effective chemotherapeutic agent for tongue cancer by targeting Notch pathway.

表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶的主要活性成分，具有低毒副作用和多种生物活性，其抗癌作用已被广泛研究。大多数研究使用癌细胞系和异种移植模型。然而，EGCG能否在癌症相关突变发生后预防肿瘤发作仍存在争议。本研究开发了Krt14-cre/ERT-Kras转基因小鼠，他莫昔芬诱导了K-RasG12D的表达。诱导两周后，K-Ras 突变小鼠在嘴唇和舌头上出现外生性肿瘤病变，Notch 信号通路显着激活。EGCG的给药有效地延迟了出现的时间，减小了肿瘤病灶的大小和重量，缓解了肿瘤病灶的异型增生，并延长老鼠的寿命。EGCG在肿瘤病灶中显着抑制Notch信号通路。此外，EGCG通过阻断Notch信号通路的激活，显着诱导细胞凋亡，抑制舌癌细胞增殖。总之，这些结果表明EGCG通过靶向Notch途径作为舌癌的有效化学治疗剂。