Oral Administration of 3,3′-Diindolylmethane Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells in BALB/c Mice
Oral Administration of 3,3′-Diindolylmethane Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells in BALB/c Mice
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DOI：
10.3945/jn.109.111864
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发表时间：
2009-12-01
影响因子：
4.2
通讯作者：
Park, Jung Han Yoon
中科院分区：
文献类型：
--
作者：
Kim, Eun Ji;Shin, Minjeong;Park, Jung Han Yoon
3，3 '-二吲哚甲烷（DIM）是十字花科蔬菜中吲哚-3-甲醇酸催化低聚反应的主要产物，具有抗癌活性。体外培养研究表明，DIM在0-10 μ mol/L浓度下呈剂量依赖性地抑制4 T1细胞的迁移、侵袭和粘附，而不伴随细胞活力的变化。在体内肺转移模型中，将4 T1细胞（2 × 10（5）个细胞/小鼠）注射到同系雌性BALB/c小鼠的尾静脉中。从第二天开始，用0-10 mg DIM/kg体重对小鼠进行管饲。d）为13 d。口服DIM给药导致肺肿瘤结节数量显著减少。DIM治疗显著降低了注射4 T1细胞的小鼠血清和肺中基质金属蛋白酶（MMP）-2，MMP-9，金属蛋白酶组织抑制剂（TIMP）-1和血管细胞粘附分子（VCAM）-1的水平，并增加了TIMP-2的水平。此外，DIM治疗降低了白细胞介素（IL）-1 β、IL-6和肿瘤坏死因子（TNF）α的血清浓度。我们已经证明，DIM深刻地抑制4 T1细胞的肺转移，这是伴随着MMP，粘附分子和促炎细胞因子的水平降低。这些结果表明，DIM具有作为抗转移剂用于治疗乳腺癌的潜力。J.营养139：2373-2379，2009.
3,3'-diindolylmethane (DIM) is the major in vivo product of the acid-catalyzed oligomerization of indole-3-carbinol present in cruciferous vegetables, and it has been shown to exhibit anticancer properties, In this study, we assessed the effects of DIM on the metastasis of 4T1 mouse mammary carcinoma cells. In vitro culture studies showed that DIM dose-dependently inhibited the migration, invasion, and adhesion of 4T1 cells at concentrations of 0-10 mu mol/L without attendant changes in cell viability. In an in vivo lung metastasis model, 4T1 cells (2 X 10(5) cells/mouse) were injected into the tail veins of syngeneic female BALB/c mice. Beginning on the second day, the mice were subjected to gavage with 0-10 mg DIM/(kg body weight . d) for 13 d. Oral DIM administration resulted in a marked reduction in the number of pulmonary tumor nodules. DIM treatment significantly reduced the levels of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1, and vascular cell adhesion molecule (VCAM)-1 and increased TIMP-2 levels in the sera and lungs of mice injected with 4T1 cells. Additionally, DIM treatment reduced the serum concentrations of interleukin (IL)-1 beta, IL-6 and tumor necrosis factor (TNF)alpha. We have demonstrated that DIM profoundly inhibits the lung metastasis of 4T1 cells, which was accompanied by reduced levels of MMP, adhesion molecules, and proinflammatory cytokines. These results indicate that DIM has potential as an antimetastatic agent for the treatment of breast cancer. J. Nutr. 139: 2373-2379, 2009.