Abstract
The antineoplastic activity of 5-aza-2'-deoxycytidine (5-AZA-CdR) and docetaxel (Taxotere, Taxo) alone or in combination against human MDA-MB-231 breast, Calu-6 lung and DU-145 prostate carcinoma cell lines was evaluated by clonogenic assay. We also investigated by RT-PCR the capacity of these agents to re-activate the expression of E-cadherin and maspin, two tumor suppressor genes that were silenced by DNA methylation. 5-AZA-CdR and Taxo in combination produced a greater loss of clonogenicity than either agent alone. In MDA-MB-231 breast carcinoma cells, Taxo did not interfere with the re-activation of E-cadherin and maspin genes by 5-AZA-CdR. These results provide a rationale for clinical trials on the combination of 5-AZA-CdR and Taxo in patients with advanced cancer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Azacitidine / analogs & derivatives*
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Azacitidine / pharmacology*
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Breast Neoplasms / genetics
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Breast Neoplasms / pathology
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Cadherins / biosynthesis
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Cadherins / genetics
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Cell Line, Tumor*
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DNA / antagonists & inhibitors
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DNA / biosynthesis
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DNA / drug effects
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Decitabine
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Docetaxel
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Dose-Response Relationship, Drug
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Drug Evaluation, Preclinical / methods*
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Female
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Gene Expression Regulation, Neoplastic / genetics
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Genes, Tumor Suppressor
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Humans
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Lung Neoplasms / pathology
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Male
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Prostatic Neoplasms / pathology
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Proteins / genetics
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Serpins / biosynthesis
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Serpins / genetics
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Taxoids / pharmacology*
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Time Factors
Substances
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Antineoplastic Agents
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Cadherins
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Proteins
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SERPIN-B5
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Serpins
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Taxoids
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Docetaxel
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Decitabine
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DNA
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Azacitidine