Abstract
The histone-lysine N-methyltransferase, enhancer of zeste homologue 2 (EZH2), functions as a transcriptional repressor and plays an important role in the development of various types of cancer. In this study, we observed the increased EZH2 expression in the Bel/FU multidrug-resistant hepatocellular carcinoma (HCC) cell line. The RNA interference (RNAi)-mediated depletion of EZH2 expression in the Bel/FU cells led to decreased multidrug resistance protein 1 (MDR1) expression, which resulted in increased apoptosis and sustained G1/S phase arrest. Moreover, siRNA targeting EZH2 sensitized Bel/FU cells to 5-fluorouracil treatment. These findings suggest that EZH2 plays a role in the development of multidrug resistance and may represent a novel therapeutic target for multidrug-resistant HCC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
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Antimetabolites, Antineoplastic / pharmacology*
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Apoptosis
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Carcinoma, Hepatocellular
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Cell Line, Tumor
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Drug Resistance, Multiple
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Drug Resistance, Neoplasm*
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Enhancer of Zeste Homolog 2 Protein
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Fluorouracil / pharmacology*
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G1 Phase Cell Cycle Checkpoints
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Gene Knockdown Techniques
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Humans
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Liver Neoplasms
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Polycomb Repressive Complex 2 / genetics*
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Polycomb Repressive Complex 2 / metabolism
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RNA Interference*
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RNA, Small Interfering / genetics
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antimetabolites, Antineoplastic
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RNA, Small Interfering
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EZH2 protein, human
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Enhancer of Zeste Homolog 2 Protein
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Polycomb Repressive Complex 2
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Fluorouracil