Sirohi Vijay Kumar, Popli Pooja, Sankhwar Pushplata, Kaushal Jyoti Bala, Gupta Kanchan, Manohar Murli, Dwivedi Anila
Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, U.P., India.
Department of Obstetrics & Gynaecology, King George's Medical University, Lucknow-226001, U.P., India.
J Nutr Biochem. 2017 Jun;44:60-70. doi: 10.1016/j.jnutbio.2016.12.021. Epub 2017 Mar 16.
Although curcumin shows anti-proliferative and anti-inflammatory activities in various cancers, the effect of curcumin on cellular migration in endometrial adenocarcinoma cells remains to be understood. The current investigation was aimed to explore the anti-proliferative and anti-migratory effects of curcumin and its mechanism of action in endometrial cancer cells. Our in-vitro and in-vivo experimental studies showed that curcumin inhibited the proliferation of endometrial cancer cells and suppressed the tumor growth in Ishikawa xenograft mouse model. Curcumin induced ROS-mediated apoptosis in endometrial cancer cells. Curcumin suppressed the migration rate of Ishikawa and Hec-1B cells as analyzed by scratch wound assay. In transwell migration studies, knock down of Slit-2 reversed the anti-migratory effect of curcumin in these cell lines. Curcumin significantly up-regulated the expression of Slit-2 in Ishikawa, Hec-1B and primary endometrial cancer cells while it down-regulated the expression of stromal cell-derived factor-1 (SDF-1) and CXCR4 which in turn, suppressed the expression of matrix metallopeptidases (MMP) 2 and 9, thus attenuating the migration of endometrial cancer cells. In summary, we have demonstrated that curcumin has inhibitory effect on cellular migration via Slit-2 mediated down-regulation of CXCR4, SDF-1, and MMP2/MMP9 in endometrial carcinoma cells. These findings helped explore the role of Slit-2 in endometrial cancer cells.
尽管姜黄素在多种癌症中显示出抗增殖和抗炎活性，但其对子宫内膜腺癌细胞迁移的影响仍有待明确。本研究旨在探讨姜黄素对子宫内膜癌细胞的抗增殖和抗迁移作用及其作用机制。我们的体外和体内实验研究表明，姜黄素可抑制子宫内膜癌细胞的增殖，并在Ishikawa异种移植小鼠模型中抑制肿瘤生长。姜黄素诱导子宫内膜癌细胞发生ROS介导的凋亡。通过划痕试验分析，姜黄素可抑制Ishikawa和Hec-1B细胞的迁移率。在Transwell迁移实验中，敲低Slit-2可逆转姜黄素对这些细胞系的抗迁移作用。姜黄素可显著上调Ishikawa、Hec-1B和原发性子宫内膜癌细胞中Slit-2的表达，同时下调基质细胞衍生因子-1（SDF-1）和CXCR4的表达，进而抑制基质金属蛋白酶（MMP）2和9的表达，从而减弱子宫内膜癌细胞的迁移。总之，我们证明了姜黄素通过Slit-2介导的CXCR4、SDF-1和MMP2/MMP9的下调对子宫内膜癌细胞的迁移具有抑制作用。这些发现有助于探索Slit-2在子宫内膜癌细胞中的作用。
