Liu Fu, Zhu Chongmei, Ma Hui, Yang Qiong
Department of Gastrointestinal Surgery, Nanyang First People's Hospital, Nanyang, 473004, China.
School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jan;397(1):109-122. doi: 10.1007/s00210-023-02584-5. Epub 2023 Jun 27.
It has been reported the anti-tumor action of curcumin on colorectal cancer. In this study, we aimed to explore the potential mechanisms underlying curcumin in the development of colorectal cancer. CCK-8, EdU, flow cytometry, and transwell invasion assays were conducted to investigate the function role of curcumin in cell proliferation, apoptosis, and invasion. The level of miR-134-5p and CDCA3 was determined using RT-qPCR analysis. Western blot was applied for detecting the levels of c-myc, MMP9, CDCA3, and CDK1. Dual-luciferase reporter assay was used to evaluate the relationship between miR-134-5p and CDCA3, and IP assay was performed to examine the interaction between CDCA3 and CDK1. Additionally, SW620 cells were injected into the mice to form the xenograft tumor model. Curcumin treatment repressed cell growth and invasion, and induced cell apoptosis in HCT-116 and SW620 cells. Curcumin elevated miR-134-5p expression and restrained CDCA3 expression in HCT-116 and SW620 cells. MiR-134-5p inhibitor or CDCA3 overexpression could restore the effects of curcumin on cell growth, apoptosis, and invasion in HCT-116 and SW620 cells. MiR-134-5p targeted CDCA3, and CDCA3 could rescue the repressive effects of miR-134-5p on the progression of colorectal cancer. Moreover, CDCA3 interacted with CDK1, and CDK1 overexpression blocked the suppressive effects of CDCA3 downregulation on the development of colorectal cancer. In addition, curcumin treatment repressed tumor growth in colorectal cancer via increasing miR-134-5p and downregulating CDCA3 and CDK1 expression in vivo. Our findings provided the evidence that curcumin upregulated miR-134-5p to inhibit the progression of colorectal cancer by regulating CDCA3/CDK1 pathway.
已有报道姜黄素对结直肠癌具有抗肿瘤作用。在本研究中，我们旨在探讨姜黄素在结直肠癌发生发展过程中的潜在机制。进行CCK-8、EdU、流式细胞术和Transwell侵袭实验，以研究姜黄素在细胞增殖、凋亡和侵袭中的作用。使用RT-qPCR分析确定miR-134-5p和CDCA3的水平。采用蛋白质免疫印迹法检测c-myc、MMP9、CDCA3和CDK1的水平。使用双荧光素酶报告基因实验评估miR-134-5p与CDCA3之间的关系，并进行免疫沉淀实验检测CDCA3与CDK1之间的相互作用。此外，将SW620细胞注射到小鼠体内以形成异种移植肿瘤模型。姜黄素处理抑制了HCT-116和SW620细胞的生长和侵袭，并诱导细胞凋亡。姜黄素提高了HCT-116和SW620细胞中miR-134-5p的表达并抑制了CDCA3的表达。miR-134-5p抑制剂或CDCA3过表达可恢复姜黄素对HCT-116和SW620细胞生长、凋亡和侵袭的影响。miR-134-5p靶向CDCA3，并且CDCA3可以挽救miR-134-5p对结直肠癌进展的抑制作用。此外，CDCA3与CDK1相互作用，并且CDK1过表达阻断了CDCA3下调对结直肠癌发展的抑制作用。另外，姜黄素处理通过在体内增加miR-134-5p并下调CDCA3和CDK1的表达来抑制结直肠癌的肿瘤生长。我们的研究结果提供了证据，表明姜黄素上调miR-134-5p以通过调节CDCA3/CDK1途径抑制结直肠癌的进展。
