Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Cell Mol Med. 2020 Sep;24(18):10648-10662. doi: 10.1111/jcmm.15683. Epub 2020 Jul 28.
Enhancer of zeste homolog 2 (EZH2), an oncogene, is a commonly up-regulated epigenetic factor in human cancer. Hepatocellular carcinoma deletion gene 1 (DLC1) is an antioncogene that is either expressed at low levels or not expressed in many malignant tumours. Curcumin is a promising anticancer drug that has antitumour effects in many tumours, but its mechanism of action is unclear. Our research demonstrated that EZH2 was up-regulated in breast cancer (BC) tissues and cells, whereas DLC1 was down-regulated, and the expression of EZH2 and DLC1 was negatively correlated in BC. By analysing the characteristics of clinical cases, we found that positive expression of EZH2 and negative expression of DLC1 may be predictors of poor prognosis in patients with triple-negative breast cancer (TNBC). Moreover, knockdown of EZH2 expression restored the expression of DLC1 and inhibited the migration, invasion and proliferation, promoted the apoptosis, and blocked the cell cycle of MDA-MB-231 cells. Furthermore, we found that curcumin restored the expression of DLC1 by inhibiting EZH2; it also inhibited the migration, invasion and proliferation of MDA-MB-231 cells, promoted their apoptosis and blocked the cell cycle. Finally, xenograft tumour models were used to demonstrate that curcumin restored DLC1 expression by inhibiting EZH2 and also inhibited the growth and promoted the apoptosis of TNBC cells. In conclusion, our results suggest that curcumin can inhibit the migration, invasion and proliferation, promote the apoptosis, block the cycle of TNBC cells and restore the expression of DLC1 by inhibiting the expression of EZH2.
增强子结合锌指蛋白 2(EZH2)是一种癌基因,是人类癌症中常见的上调表观遗传因子。肝细胞癌缺失基因 1(DLC1)是一种抑癌基因,在许多恶性肿瘤中表达水平低或不表达。姜黄素是一种很有前途的抗癌药物,在许多肿瘤中都有抗肿瘤作用,但作用机制尚不清楚。我们的研究表明,EZH2 在乳腺癌(BC)组织和细胞中上调,而 DLC1 下调,并且 EZH2 和 DLC1 的表达在 BC 中呈负相关。通过分析临床病例的特点,我们发现 EZH2 阳性表达和 DLC1 阴性表达可能是三阴性乳腺癌(TNBC)患者预后不良的预测指标。此外,敲低 EZH2 表达可恢复 DLC1 的表达,并抑制 MDA-MB-231 细胞的迁移、侵袭和增殖,促进凋亡,阻断细胞周期。此外,我们发现姜黄素通过抑制 EZH2 恢复了 DLC1 的表达;它还抑制了 MDA-MB-231 细胞的迁移、侵袭和增殖,促进其凋亡并阻断细胞周期。最后,使用异种移植肿瘤模型证明,姜黄素通过抑制 EZH2 恢复 DLC1 的表达,同时抑制 TNBC 细胞的生长并促进其凋亡。总之,我们的研究结果表明,姜黄素通过抑制 EZH2 的表达,可抑制 TNBC 细胞的迁移、侵袭和增殖,促进其凋亡,阻断细胞周期,并恢复 DLC1 的表达。