Estrogen induced metastatic modulators MMP-2 and MMP-9 are targets of 3,3'-diindolylmethane in thyroid cancer.
Estrogen induced metastatic modulators MMP-2 and MMP-9 are targets of 3,3'-diindolylmethane in thyroid cancer.
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雌激素诱导的转移性调节剂MMP-2和MMP-9是甲状腺癌中3,3'-二迪丁甲烷的靶标。
DOI：
10.1371/journal.pone.0015879
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发表时间：
2011-01-18
期刊：
影响因子：
3.7
通讯作者：
Tiwari RK
中科院分区：
文献类型：
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作者：
Rajoria S;Suriano R;George A;Shanmugam A;Schantz SP;Geliebter J;Tiwari RK
甲状腺癌是最常见的内分泌相关癌症，在过去五年中发病率不断上升。目前甲状腺癌的治疗方法，如手术或放射性碘治疗，通常需要患者终身接受甲状腺激素替代治疗，并且鉴于甲状腺癌的显著复发率，需要新的预防方法。本研究探讨了在十字花科蔬菜中发现的天然膳食化合物3，3 ′-二吲哚甲烷（DIM）通过功能性雌激素受体靶向甲状腺癌细胞转移表型的特性。采用雌激素和（或）DIM处理甲状腺癌细胞株，并通过体外粘附、迁移和侵袭实验研究DIM的抗转移和抗雌激素作用。我们观察到DIM抑制雌激素介导的甲状腺癌细胞迁移、粘附和侵袭的增加，这也得到ER-α下调（siRNA）研究的支持。蛋白质印迹和酶谱分析提供了直接的证据，这种DIM介导的E2增强的转移相关事件的抑制，凭借靶向必需的蛋白水解酶，即MMP-2和MMP-9。我们的数据首次报道DIM通过抑制雌二醇增强的甲状腺癌细胞增殖和体外转移相关事件，即粘附、迁移和侵袭，显示抗雌激素样活性。最重要的是，MMP-2和MMP-9，这是已知的促进和增强转移，被确定为DIM的目标。这种抗雌激素样的性质DIM可能会导致一种新的预防和/或治疗性的膳食补充剂的甲状腺癌患者通过靶向疾病的进展的发展。
Thyroid cancer is the most common endocrine related cancer with increasing incidences during the past five years. Current treatments for thyroid cancer, such as surgery or radioactive iodine therapy, often require patients to be on lifelong thyroid hormone replacement therapy and given the significant recurrence rates of thyroid cancer, new preventive modalities are needed. The present study investigates the property of a natural dietary compound found in cruciferous vegetables, 3,3′-diindolylmethane (DIM), to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor. Thyroid cancer cell lines were treated with estrogen and/or DIM and subjected to in vitro adhesion, migration and invasion assays to investigate the anti-metastatic and anti-estrogenic effects of DIM. We observed that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA) studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E2 enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9. Our data reports for the first time that DIM displays anti-estrogenic like activity by inhibiting estradiol enhanced thyroid cancer cell proliferation and in vitro metastasis associated events, namely adhesion, migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were determined to be targets of DIM. This anti-estrogen like property of DIM may lead to the development of a novel preventive and/or therapeutic dietary supplement for thyroid cancer patients by targeting progression of the disease.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
雌激素 G 蛋白偶联受体 30 信号传导通过 MEK/ERK 丝裂原激活蛋白激酶途径促进增殖、侵袭潜力和白细胞介素 6 分泌，从而参与子宫内膜癌的调节
影响因子：
5.7
作者：
He, Yin-Yan;Cai, Bin;Wan, Xiao-Ping
通讯作者：
Wan, Xiao-Ping
影响因子：
4.1
作者：
Márquez, DC;Chen, HW;Pietras, RJ
通讯作者：
Pietras, RJ
DOI：
10.1016/j.bbrc.2005.12.059
发表时间：
2006-02-10
影响因子：
3.1
作者：
Garikapaty, VPS;Ashok, BT;Tiwari, RK
通讯作者：
Tiwari, RK
DOI：
10.1038/nrc2646
发表时间：
2009-07
期刊：
Nature reviews. Cancer
影响因子：
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作者：
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