Abstract
The aim of this study was to evaluate whether emodin can overcome the chemoresistance of the gemcitabine-resistant cancer cell line (Bxpc-3/Gem) in vitro. The cell line Bxpc-3/Gem was derived from the human pancreatic cancer cell line Bxpc-3. We found that Bxpc-3/Gem cells were characterized by a series of morphological changes with a resistance index of 43.51 comparing with the parental cell line. Emodin reduced Bxpc-3/Gem cell proliferation in a dose-dependent manner. Emodin and gemcitabine combination treatments resulted in decreased cell proliferation and increased apoptosis in Bxpc-3/Gem cells. In addition, combination treatments resulted in downregulation of gene and protein expression of MDR-1 (P-gp), NF-κB, XIAP, survivin, as well as inhibition of NF-κB activity and P-gp function. These observations suggest that emodin may sensitize the pancreatic cancer gemcitabine-resistant cell line Bxpc-3/Gem to gemcitabine therapy via inhibition of survival signaling.
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, 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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Caspase 3 / genetics
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Caspase 3 / metabolism
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Caspase 9 / genetics
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Caspase 9 / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Shape / drug effects
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Deoxycytidine / analogs & derivatives*
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Deoxycytidine / pharmacology
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Down-Regulation
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Drug Resistance, Neoplasm / drug effects*
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Drug Synergism
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Emodin / pharmacology*
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Gemcitabine
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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Inhibitor of Apoptosis Proteins / genetics
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Inhibitor of Apoptosis Proteins / metabolism
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Inhibitory Concentration 50
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NF-kappa B / metabolism*
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Protein Binding
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Survivin
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X-Linked Inhibitor of Apoptosis Protein / genetics
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X-Linked Inhibitor of Apoptosis Protein / metabolism
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antimetabolites, Antineoplastic
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BIRC5 protein, human
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Inhibitor of Apoptosis Proteins
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NF-kappa B
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Survivin
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X-Linked Inhibitor of Apoptosis Protein
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XIAP protein, human
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Deoxycytidine
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CASP3 protein, human
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CASP9 protein, human
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Caspase 3
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Caspase 9
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Emodin
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Gemcitabine