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Soy Isoflavones Inhibit the Proliferation of Human Breast Cancer MCF-7 Cells Via the Activation of PPARγ

Author: RongZuo
Tutor: ZhuJunDong
School: Third Military Medical University
Course: Nutrition and Food Hygiene
Keywords: Soy isoflavones Rosiglitazone Breast cancer cells Peroxisome proliferator-activated receptor γ Cell proliferation Cell cycle GW9662 PTEN cyclinB cyclinD1 p21
CLC: R737.9
Type: Master's thesis
Year: 2011
Downloads: 94
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Abstract


Breast cancer is one of the most common malignant tumors of the serious threat to women's lives and health. Dietary factors play an important role in the incidence of breast cancer in the evolution of concern, including soybeans and their products on the protective effect of breast cancer research, and that the phytochemicals in soy ingredients soy isoflavones (soy isoflavones, SI) its protective effect of the main active ingredient. SI including genistein (genistein, GEN) and daidzein (daidzein, DAI) two main components, its molecular structure is very similar to the characteristics of the human endogenous estrogen structure, with members of the nuclear receptor superfamily estrogen receptor (estrogen receptor, ER), which has the analog estrogenic effects and the role of estrogen antagonistic dual regulatory activity, called phytoestrogens. In recent years, scholars of SI's anti-breast cancer effect of a large number of animal experiments and in vitro studies, the results showed that SI has the following anti-tumor effect: (1) block cell cycle progression, and inhibition of tumor cell proliferation; (2) induce apoptosis in tumor cells; (3) inhibition of tumor cell invasion and metastasis; (4) to inhibit tumor angiogenesis, reduce tumor microvessel density (Microvessel density, MVD) to stop tumor growth. SI target for anti-breast cancer gene including cyclin B, p21, p16, Bax, Bcl-2, NF-κB, Akt, MMPs, but SI regulation of target gene expression molecular mechanisms are not yet fully elucidated. Peroxisome proliferator-activated receptors (Peroxisome proliferator-activated receptors, PPARs) belong to one of the members of the nuclear receptor superfamily. PPARs include the PPARα, PPARβ and PPARγ3 one of subtypes, PPARs as ligand-dependent activation of nuclear transcription regulatory factors in conjunction with the corresponding ligand activated after and peroxisome proliferation in the target gene promoter material response element ( Peroxisome proliferator response element, PPRE), thereby regulating the expression level of the target gene involved in cell physiological function regulator. Recent studies have found that most of the tumor cells are present PPARγ expression of PPARγ relationship between the tumor began to receive widespread attention. A large number of in vitro and in vivo experimental results show that some PPARγ ligands such as glitazones, rosiglitazone (rosiglitazone, ROS), prostaglandin metabolite 15-d-PGJ2 on breast cancer, prostate cancer, colon cancer, liver cancer, tumors of the lung, stomach and other organs sources have significant anti-tumor effect, therefore PPARγ is considered a new target for cancer treatment, PPARγ ligands may be potential tumor chemical control drugs. Has an initial study confirmed that SI can be used as natural ligands of PPARγ. SI anti-breast cancer is associated with the PPARγ signaling pathway is unclear. Based on the above analysis, this study chose breast cancer cell line MCF-7 cells as experimental subjects, Immunocytochemistry PPRE-driven luciferase reporter gene assay, CCK-8 the colorimetry, cell cycle analysis, Western blot (Western blot) and other technical methods, the first observation of human breast cancer MCF-7 cells the expression of PPARγ, as well as GEN, DAI and ROS (as a positive control) activation of PPARγ in MCF-7 cells, and then compare GEN, DAI and ROS alone or in combination with PPARγ-specific antagonist GW9662 treatment of MCF-7 cells, cell proliferation and cell cycle, and regulation of cell proliferation gene PTEN cyclinB changes in protein expression levels of cyclin D1, p21, etc., in order to explore the PPARγ signaling pathway in soybean isoflavones inhibit the growth of breast cancer cells. The main findings and conclusions are as follows: 1.PPARγ Immunocytochemistry results showed brownish yellow or tan colored particles are visible in the cytoplasm and nucleus of breast cancer MCF-7 cells, and the colored particles are mainly distributed in the cytoplasm in. The results indicate that breast cancer MCF-7 cells with PPARγ expression. Driven luciferase reporter gene assay 2.PPRE analysis showed that, GEN, DAI and ROS can significantly enhance breast cancer MCF-7 cells, luciferase reporter gene activity (p lt; 0.05) and PPARγ specific inhibition agent GW9662 significantly reversed GEN to DAI and ROS luciferase reporter gene expression in MCF-7 cells with increased activity of the role. The results show, GEN DAI, and ROS can activate PPARγ signaling pathway in breast cancer MCF-7 cells. 3.CCK-8 colorimetric assay of cell proliferation results show 8 x 10-5 mol / L GEN, DAI and 1 × 10-5 mol / L ROS can significantly inhibit breast cancer MCF-7 cell proliferation (p lt; 0.05), and there is a time-dependent effect. PPARγ-specific inhibitor GW9662 significantly weaken GEN, DAI and ROS inhibition of proliferation of MCF-7 cells (p lt; 0.05). The results show that, GEN, DAI and ROS inhibits the proliferation of MCF-7 cells and its activation of PPARγ signaling pathways. Flow cytometry analysis showed GEN, the DAI deal with breast cancer MCF-7 cells can lead to the G2 / M phase arrest, ROS treatment caused cell cycle arrest in G0/G1 phase. PPARγ-specific inhibitor GW9662 significantly weakened GEN, DAI and ROS MCF-7 cell cycle arrest (p lt; 0.05). The results show that, GEN, DAI and ROS PPARγ signaling pathway through the activation of MCF-7 cells, causing cell cycle arrest. Protein detected by Western blotting analysis results, GEN DAI, and ROS can significantly increase breast cancer MCF-7 cells of PTEN and p21 protein expression levels, GEN and DAI significantly lower cyclinB, cyclinD1 protein expression levels, and ROS only significantly reduced cyclinD1 protein expression levels. PPARγ-specific inhibitor GW9662 significantly weaken GEN, DAI and ROS in MCF-7 cells of PTEN cyclinB of cyclinD1, p21 protein levels increase or reduce the role. The results show that, GEN, DAI and ROS can activate PPARγ signaling pathways of MCF-7 cells, causing cell cycle regulation gene protein expression levels change significantly. These results suggest that human breast cancer MCF-7 cells expression of PPARγ, SI two main ingredients DEN and DAI MCF-7 cells can activate PPARγ signaling pathway, causing cell proliferation regulatory gene PTEN cyclinB of cyclin D1, P21 protein The expression levels change significantly, resulting in G2 / M phase arrest, thereby inhibiting the proliferation of MCF-7 cells. The preliminary experimental findings confirmed the activation of PPARγ signaling pathway is one of the molecular mechanisms mediated SI anti-breast cancer.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Breast tumor
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