Wu Hao, Zhou Jingcheng, Zeng Chao, Wu Da, Mu Zhimin, Chen Baokun, Xie Yuancai, Ye Yiwang, Liu Jixian
Department of Thoracic Surgery, Peking University Shenzhen Hospital, Shenzhen 518036, Guangdong Province, China.
Oncotarget. 2016 Dec 27;7(52):87081-87090. doi: 10.18632/oncotarget.13499.
Curcumin is a novel drug for lung cancer treatment. However, the mechanism underlying the anti-tumor effect of curcumin remains elusive. Previous evidences indicated that, the methylating transferase DNMT1 is downregulated by curcumin, and the transcription factor 21 (TCF21) is suppressed by DNMT1. We hereby attempt to elucidate the correlation between curcumin treatment and TCF21 expression. Exosomes derived from curcumin-pretreated H1299 cells were used to treat BEAS-2B cells, which induced proliferation, colony formation and migration of BEAS-2B cells. An increase in TCF21 expression in response to curcumin was also seen, as revealed by real-time PCR (RT-PCR) and western blot. Analysis using the GEO database (access #GSE21210) indicated that a positive correlation existed between TCF21 levels and lung cancer patient survival. TCF21 overexpression and knockdown was introduced to H1299 cells through lentiviral system, which led to suppression and promotion of tumor growth, respectively. We also demonstrated that DNMT1 expression was downregulated by curcumin. Therefore, curcumin exerts its anti-cancer function by downregulating DNMT1, thereby upregulating TCF21.
姜黄素是一种用于肺癌治疗的新型药物。然而，姜黄素抗肿瘤作用的潜在机制仍不清楚。先前的证据表明，姜黄素可下调甲基转移酶DNMT1，而转录因子21（TCF21）受DNMT1抑制。我们在此试图阐明姜黄素治疗与TCF21表达之间的相关性。用姜黄素预处理的H1299细胞来源的外泌体处理BEAS-2B细胞，可诱导BEAS-2B细胞增殖、集落形成和迁移。实时定量聚合酶链反应（RT-PCR）和蛋白质免疫印迹法显示，姜黄素处理后TCF21表达增加。使用GEO数据库（访问编号#GSE21210）分析表明，TCF21水平与肺癌患者生存率呈正相关。通过慢病毒系统将TCF21过表达和敲低导入H1299细胞，分别导致肿瘤生长受到抑制和促进。我们还证明姜黄素可下调DNMT1表达。因此，姜黄素通过下调DNMT1发挥抗癌作用，从而上调TCF21。
