张晓梅 赵玉涛 王菊美 赵社芬 韩坤岭 李艳霞 韩雪 范秀敏

摘要 目的：探究姜黃素对结直肠癌细胞增殖、迁移、侵袭以及上皮间质转化的影响。方法：取结直肠癌HCT116细胞系，随机分为对照组和观察组，观察组细胞使用姜黄素50 μg/mL处理，对照组给予等量二甲基亚砜处理;采用噻唑蓝（MTT）法检测细胞增殖;划痕愈合实验检测细胞迁移;Transwell实验检测细胞侵袭;蛋白免疫印迹法（Western Blotting）检测细胞中上皮性钙黏蛋白（E-cadherin）、神经性钙黏蛋白（N-cadherin）、波形蛋白（Vimentin）、磷酸化Jagged 1蛋白（p-JAG1）、磷酸化Notch受体1蛋白（p-Notch1）以及磷酸化Notch受体2蛋白（p-Notch2）表达水平。结果：MTT法检测显示，姜黄素可显著抑制HCT116细胞增殖。划痕愈合实验以及Transwell实验显示姜黄素可显著抑制HCT116细胞迁移及侵袭。Western Blotting实验显示姜黄素可增加E-cadherin蛋白表达水平，降低N-cadherin和Vimentin蛋白以及p-JAG1、p-Notch1、p-Notch2等蛋白的表达水平（均P<0.05）。结论：姜黄素可显著抑制结直肠癌HCT116细胞增殖、迁移、侵袭以及上皮间质转化，其机制可能与JAG1/Notch2通路失活有关。

关键词 姜黄素;结直肠癌;增殖;迁移;侵袭;上皮-间质转化

Effects and Mechanism of Curcumin on Cell Migration，Invasion，and Epithelial-Mesenchymal Transformation in Colorectal Cancer Cells

ZHANG Xiaomei1，ZHAO Yutao1，WANG Jumei1，ZHAO Shefen1，HAN Kunling1，LI Yanxia2，HAN Xue3，FAN Xiumin4

（1 Handan Central Hospital，Handan 056001，China; 2 Department of General Surgery，Affiliated Hospital of Hebei Engineering University，Handan 056002，China; 3 Department of Pharmacy，Hebei University of Chinese Medicine，Shijiazhuang 050200，China; 4 Department of Hematology，Handan First Hospital，Handan 056002，China）

Abstract Objective：To investigate the effects of curcumin on the proliferation，migration，invasion and epithelial mesenchymal transformation（EMT） of colorectal cancer cells.Methods：HCT116 cell lines of colorectal cancer were taken and randomly divided into a control group and an intervention group.HCT116 cells in intervention group were treated with curcumin 50 Ug/mL，and HCT116 cells in control group were treated with the same amount of dimethyl sulfoxide.The cell proliferation ability was detected by thiazolium blue（MTT） assay.Cell migration ability was detected by scratch healing assay.Cell invasion ability was detected by Transwell assay.Expression levels of epithelial cadherin（E-cadherin），neuronal cadherin（N-cadherin），Vimentin，p-Jagged 1（p-JAG1），p-Notch receptor 1（p-Notch 1），and p-Notch receptor 2（p-Notch2） were detected by Western Blotting.Results：Detection of MTT assay showed that curcumin could significantly inhibit the proliferation of HCT116 cells.Wounding healing assay and Transwell assay showed that curcumin could significantly inhibit HCT116 cell migration and invasion.Western Blotting experiments showed that curcumin could increase the expression level of E-cadherin protein，and decrease the expression levels of N-cadherin and Vimentin proteins，as well as p-JAG1，p-Notch1，p-Notch2 and other proteins（P<0.05）.Conclusion：Curcumin can significantly inhibit the proliferation，migration，invasion and epithelial mesenchymal transformation of colorectal cancer HCT116 cells，and the mechanism may be related to the inactivation of JAG1/Notch2 pathway.

Keywords Curcumin; Colorectal cancer; Proliferation; Migration; Invasion; Epithelial-mesenchymal transformation

中图分类号：R284;R735.3文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.17.014

结直肠癌（Colorectal Cancer，CRC）是一种常见的恶性肿瘤，每年全世界CRC死亡病例超过60万，并且约25%的CRC患者在确诊时已经出现远处转移[1-2]。晚期CRC患者的预后较差，5年生存率不超过10%[3]。目前越来越多的研究证实某些中草药可用于肿瘤的治疗[4]。姜黄素是从中药姜黄中提取的一种有效活性成分，具有抗氧化、抗炎、清除自由基以及抗肿瘤等多种药理作用，常应用于心血管疾病以及消化系统疾病的治疗[5-6]。已有研究发现，姜黄素可抑制CRC致瘤性激酶PBK的活性，降低HCT116细胞的增殖水平，并诱导细胞凋亡[7]。然而，姜黄素对CRC细胞迁移、侵袭和上皮间质转化（Epithelial-mesenchymal Transition，EMT）中的作用和具体机制尚不清楚。……