Zhang Li, Cheng Xian, Gao Yanyan, Zhang Chiyu, Bao Jiandong, Guan Haixia, Yu Huixin, Lu Rongrong, Xu Qiang, Sun Yang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China; Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu, China.
Exp Cell Res. 2016 Feb 15;341(2):157-65. doi: 10.1016/j.yexcr.2016.01.006. Epub 2016 Jan 27.
Thyroid cancers usually possess a good prognosis while the risks of recurrence and metastasis turn out to be a disturbing issue. Curcumin [bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione] is a natural polyphenolic compound mainly found in turmeric (Curcuma longa). Our previous studies have demonstrated that curcumin showed proliferation-inhibitory and apoptosis-inducing effects on K1 papillary thyroid cancer cells. However, the mechanism underlying the inhibition effects of curcumin on thyroid cancer cells remains unclear. Herein, we demonstrated that curcumin remarkably increased the expression of the epithelial marker E-cadherin and repressed the expression of the mesenchymal marker vimentin in human papillary thyroid carcinoma BCPAP cells. Curcumin also suppressed multiple metastatic steps of BCPAP cells, including cell attachment, spreading as well as migration. In addition, the transcription, secretion and activation of matrix metalloproteinases (MMPs) induced by transforming growth factor-β1 (TGF-β1) in BCPAP cells were mitigated upon curcumin treatment. Further evidence showed that curcumin decreased TGF-β1-mediated phosphorylation of Smad2 and Smad3. These results revealed that curcumin inhibited the TGF-β1-induced epithelial-mesenchymal transition (EMT) via down-regulation of Smad2/3 signaling pathways. Our findings provide new evidence that the anti-metastatic and anti-EMT activities of curcumin may contribute to the development of chemo-preventive agents for thyroid cancer treatment.
甲状腺癌通常预后良好，但其复发和转移风险却是一个令人困扰的问题。姜黄素[双（4-羟基-3-甲氧基苯基）-1,6-庚二烯-3,5-二酮]是一种主要存在于姜黄（姜黄属植物）中的天然多酚化合物。我们之前的研究表明，姜黄素对K1乳头状甲状腺癌细胞具有增殖抑制和凋亡诱导作用。然而，姜黄素对甲状腺癌细胞抑制作用的潜在机制仍不清楚。在此，我们证明姜黄素显著增加人乳头状甲状腺癌BCPAP细胞中上皮标志物E-钙黏蛋白的表达，并抑制间充质标志物波形蛋白的表达。姜黄素还抑制BCPAP细胞的多个转移步骤，包括细胞黏附、铺展以及迁移。此外，姜黄素处理后，BCPAP细胞中由转化生长因子-β1（TGF-β1）诱导的基质金属蛋白酶（MMPs）的转录、分泌和激活均得到缓解。进一步的证据表明，姜黄素降低了TGF-β1介导的Smad2和Smad3的磷酸化。这些结果表明，姜黄素通过下调Smad2/3信号通路抑制TGF-β1诱导的上皮-间质转化（EMT）。我们的研究结果提供了新的证据，表明姜黄素的抗转移和抗EMT活性可能有助于开发用于甲状腺癌治疗的化学预防剂。
