Abstract
To investigate the therapeutic effect of methylselenocysteine (MSC) combined with tamoxifen in MCF-7 breast cancer xenograft and the underlying mechanisms. MCF-7 breast cancer xenograft was established in ovariectomized female athymic nude mice and treated with tamoxifen and/or MSC. Tumor size was measured twice a week. Immunohistochemistry and TUNEL assays were used to measure ERalpha expression, ERalpha target genes (progesterone receptor (PR) and cyclin D1 expression), Ki-67 index, apoptosis and microvessel density. Combined treatment with tamoxifen and MSC synergistically inhibited tumor growth compared to MSC alone and tamoxifen alone. MSC alone or MSC + tamoxifen significantly reduced ERalpha, PR and cyclin D1, Ki67 index and microvessel density while increasing apoptosis in tumor tissues. These findings demonstrate synergistic growth inhibition of ERalpha positive breast cancer xenografts by combination of tamoxifen with organic selenium compounds. Organic selenium may provide added benefit when combined with tamoxifen in adjuvant therapy or prevention.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / blood supply
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology
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Angiogenesis Inhibitors / therapeutic use*
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Animals
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Apoptosis / drug effects*
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Breast Neoplasms / blood supply
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Cell Division / drug effects
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Cyclin D1 / biosynthesis
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Cyclin D1 / genetics
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Cysteine / administration & dosage
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Cysteine / analogs & derivatives*
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Cysteine / pharmacology
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Drug Synergism
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Estradiol* / toxicity
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Estrogen Receptor alpha / biosynthesis
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Estrogen Receptor alpha / genetics
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Mice
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Mice, Nude
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Neoplasm Proteins / biosynthesis
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Neoplasm Proteins / genetics
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Neoplasms, Hormone-Dependent / blood supply
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Neoplasms, Hormone-Dependent / drug therapy*
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Neoplasms, Hormone-Dependent / metabolism
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Neoplasms, Hormone-Dependent / pathology
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Neovascularization, Pathologic / drug therapy*
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Organoselenium Compounds / administration & dosage
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Organoselenium Compounds / pharmacology*
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Random Allocation
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Receptors, Progesterone / biosynthesis
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Receptors, Progesterone / genetics
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Selenocysteine / analogs & derivatives
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Specific Pathogen-Free Organisms
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Tamoxifen / administration & dosage
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Xenograft Model Antitumor Assays
Substances
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Angiogenesis Inhibitors
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CCND1 protein, human
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ESR1 protein, human
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Estrogen Receptor alpha
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Neoplasm Proteins
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Organoselenium Compounds
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Receptors, Progesterone
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Tamoxifen
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Selenocysteine
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Cyclin D1
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Estradiol
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Cysteine
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selenomethylselenocysteine