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3,3'-二吲哚甲烷通过联合抑制 ERK 和 AKT 通路抑制人癌细胞的迁移和侵袭。

3,3'-diindolylmethane inhibits migration and invasion of human cancer cells through combined suppression of ERK and AKT pathways.

机构信息

Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, NY 10595, USA.

出版信息

Oncol Rep. 2011 Feb;25(2):491-7. doi: 10.3892/or.2010.1076. Epub 2010 Dec 7.

DOI:10.3892/or.2010.1076
PMID:21152869
Abstract

Metastasis of cancer is a multifactorial disease and is the main cause of death in patients with malignancy. This disease demands treatments which may target multiple dysregulated cellular pathways in cancer cells. The anti-tumor and anti-metastatic properties of natural products in cancer prevention have been confirmed by several epidemiological studies, with cruciferous vegetables being especially protective against many cancers. In this study, we evaluated the anti-carcinogenic effects of 3,3'-diindolylmethane (DIM), which is a bioactive compound present in cruciferous vegetables and a widely used dietary supplement, on events commonly observed during metastasis using in vitro adhesion, migration and invasion assays. Our results indicate that DIM inhibits human cancer cell in vitro proliferation, adhesion, migration and invasion. Western blot analyses show that this inhibition of cell proliferation by DIM is exerted by combined suppression of AKT and ERK pathways. Furthermore, DIM also leads to down-regulation of G1-S cell cycle markers: cyclin D1, cdk6 and cdk4. These findings may lead to development of a novel preventive and/or therapeutic dietary supplement for patients diagnosed with cancer or predisposed to developing certain cancers.

摘要

癌症转移是一种多因素疾病,是恶性肿瘤患者死亡的主要原因。这种疾病需要针对癌细胞中多个失调的细胞途径进行治疗。几项流行病学研究证实了天然产物在癌症预防中的抗肿瘤和抗转移特性,十字花科蔬菜尤其能预防多种癌症。在这项研究中,我们评估了 3,3'-二吲哚甲烷(DIM)的抗癌作用,DIM 是十字花科蔬菜中的一种生物活性化合物,也是一种广泛使用的膳食补充剂,通过体外黏附、迁移和侵袭试验来研究其对转移过程中常见事件的影响。我们的结果表明,DIM 抑制人癌细胞的体外增殖、黏附、迁移和侵袭。Western blot 分析表明,DIM 通过联合抑制 AKT 和 ERK 通路来抑制细胞增殖。此外,DIM 还导致 G1-S 细胞周期标志物:cyclin D1、cdk6 和 cdk4 的下调。这些发现可能为诊断患有癌症或易患某些癌症的患者开发一种新的预防和/或治疗性膳食补充剂提供依据。

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