Tong Weihua, Wang Quan, Sun Donghui, Suo Jian
Department of Gastrointestinal-Colorectal Surgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Lett. 2016 Nov;12(5):4139-4146. doi: 10.3892/ol.2016.5148. Epub 2016 Sep 16.
Curcumin, an active nontoxic ingredient of turmeric, possesses potent anti-inflammatory, antioxidant and anti-cancer properties; however, the molecular mechanisms of curcumin are not fully understood. The transcription factor nuclear factor-κB (NF-κB) is key in cellular processes, and the expression/activation of urokinase-type plasminogen activator (uPA) and matrix metalloproteinase-9 (MMP9) are crucial for cell invasion. The present study investigated the hypothesis that curcumin inhibits colon cancer cell invasion by modulating NF-κB-mediated expression and activation of uPA and MMP9. Human colon cancer SW480 and LoVo cells were treated with various concentrations of curcumin. Curcumin was demonstrated to dose-dependently inhibit the adhesion and proliferation ability of LoVo and SW480 cells using Transwell and MTT assays, respectively. In addition, curcumin activated 5' AMP-activated protein kinase (AMPK) and suppressed p65 NF-κB phosphorylation, as shown by western blot analysis. Compound C, a potent AMPK inhibitor, abolished curcumin-induced inhibition of NF-κB, uPA and MMP9, suggesting that AMPK activation is responsible for curcumin-mediated NF-κB, uPA and MMP9 inhibition. The binding activity of NF-κB to DNA was examined and western blotting and quantitative polymerase reaction was performed to detect the effect of curcumin on the expression of uPA and MMP9. The present results revealed that curcumin significantly decreased the expression of uPA and MMP9 and NF-κB DNA binding activity. Furthermore, curcumin decreased the level of the p65 subunit of NF-κB binding to the promoter of the gene encoding uPA and MMP9, which suppressed transcriptional activation of uPA and MMP9. Overall, the present data suggest that curcumin inhibits colon cancer cell invasion via AMPK activation and subsequent inhibition of p65 NF-κB, uPA and MMP9. The therapeutic potential of curcumin for colon cancer metastasis required additional study.
姜黄素是姜黄中的一种活性无毒成分，具有强大的抗炎、抗氧化和抗癌特性；然而，姜黄素的分子机制尚未完全明确。转录因子核因子-κB（NF-κB）在细胞过程中起关键作用，尿激酶型纤溶酶原激活物（uPA）和基质金属蛋白酶-9（MMP9）的表达/激活对细胞侵袭至关重要。本研究探讨了姜黄素通过调节NF-κB介导的uPA和MMP9的表达及激活来抑制结肠癌细胞侵袭的假说。用不同浓度的姜黄素处理人结肠癌细胞SW480和LoVo细胞。分别通过Transwell和MTT试验证明，姜黄素能剂量依赖性地抑制LoVo和SW480细胞的黏附及增殖能力。此外，蛋白质免疫印迹分析显示，姜黄素可激活5'单磷酸腺苷激活的蛋白激酶（AMPK）并抑制p65 NF-κB磷酸化。强效AMPK抑制剂化合物C消除了姜黄素诱导的对NF-κB、uPA和MMP9的抑制作用，表明AMPK激活是姜黄素介导的对NF-κB、uPA和MMP9抑制的原因。检测了NF-κB与DNA的结合活性，并进行蛋白质免疫印迹和定量聚合酶反应以检测姜黄素对uPA和MMP9表达的影响。目前的结果表明，姜黄素显著降低了uPA和MMP9的表达以及NF-κB与DNA的结合活性。此外，姜黄素降低了与uPA和MMP9编码基因启动子结合的NF-κB的p65亚基水平，从而抑制了uPA和MMP9的转录激活。总体而言，目前的数据表明，姜黄素通过激活AMPK以及随后抑制p65 NF-κB、uPA和MMP9来抑制结肠癌细胞侵袭。姜黄素对结肠癌转移的治疗潜力还需要进一步研究。
