Hou Yingying, Feng Shaoyan, Wang Lixia, Zhao Zhe, Su Jingna, Yin Xuyuan, Zheng Nana, Zhou Xiuxia, Xia Jun, Wang Zhiwei
The Cyrus Tang Hematology Center and Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China.
Department of Otolaryngology, Head and Neck Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
Oncotarget. 2017 Jul 8;8(37):62120-62130. doi: 10.18632/oncotarget.19097. eCollection 2017 Sep 22.
Recent studies have revealed that rottlerin is a natural chemical drug to exert its anti-cancer activity. However, the molecular mechanisms of rottlerin-induced tumor suppressive function have not been fully elucidated. Notch signaling pathway has been characterized to play a crucial role in tumorigenesis. Therefore, regulation of Notch pathway could be beneficial for the treatment of human cancer. The aims of our current study were to explore whether rottlerin could suppress Notch-1 expression, which leads to inhibition of cell proliferation, migration and invasion in nasopharyngeal carcinoma cells. We performed several approaches, such as CTG, Flow cytometry, scratch healing assay, transwell and Western blotting. Our results showed that rottlerin treatment inhibited cell growth, migration and invasion, and triggered apoptosis, and arrested cell cycle to G1 phase. Moreover, the expression of Notch-1 was obvious decreased in nasopharyngeal carcinoma cells after rottlerin treatment. Importantly, overexpression of Notch-1 promoted cell growth and invasion, whereas down-regulation of Notch-1 inhibited cell growth and invasion in nasopharyngeal carcinoma cells. Notably, we found the over-expression of Notch-1 could abrogate the anti-cancer function induced by rottlerin. Strikingly, our study implied that Notch-1 could be a useful target of rottlerin for the prevention and treatment of human nasopharyngeal carcinoma.
最近的研究表明，rottlerin是一种具有抗癌活性的天然化学药物。然而，rottlerin诱导肿瘤抑制功能的分子机制尚未完全阐明。Notch信号通路在肿瘤发生过程中起着关键作用。因此，调节Notch通路可能对人类癌症的治疗有益。我们当前研究的目的是探讨rottlerin是否能抑制Notch-1表达，从而抑制鼻咽癌细胞的增殖、迁移和侵袭。我们采用了多种方法，如CTG、流式细胞术、划痕愈合试验、Transwell实验和蛋白质免疫印迹法。我们的结果表明，rottlerin处理可抑制细胞生长、迁移和侵袭，并引发细胞凋亡，使细胞周期停滞在G1期。此外，rottlerin处理后鼻咽癌细胞中Notch-1的表达明显降低。重要的是，Notch-1的过表达促进细胞生长和侵袭，而Notch-1的下调则抑制鼻咽癌细胞的生长和侵袭。值得注意的是，我们发现Notch-1的过表达可以消除rottlerin诱导的抗癌功能。令人惊讶的是，我们的研究表明，Notch-1可能是rottlerin预防和治疗人类鼻咽癌的一个有用靶点。
