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
- Research Support, Non-U.S. Gov't
MeSH terms
- ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
- ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
- Antimetabolites, Antineoplastic / pharmacology*
- Apoptosis
- Caspase 3 / genetics
- Caspase 3 / metabolism
- Caspase 9 / genetics
- Caspase 9 / metabolism
- Cell Line, Tumor
- Cell Proliferation / drug effects
- Cell Shape / drug effects
- Deoxycytidine / analogs & derivatives*
- Deoxycytidine / pharmacology
- Down-Regulation
- Drug Resistance, Neoplasm / drug effects*
- Drug Synergism
- Emodin / pharmacology*
- Gemcitabine
- Gene Expression Regulation, Neoplastic / drug effects*
- Humans
- Inhibitor of Apoptosis Proteins / genetics
- Inhibitor of Apoptosis Proteins / metabolism
- Inhibitory Concentration 50
- NF-kappa B / metabolism*
- Protein Binding
- Survivin
- X-Linked Inhibitor of Apoptosis Protein / genetics
- X-Linked Inhibitor of Apoptosis Protein / metabolism
Substances
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antimetabolites, Antineoplastic
- BIRC5 protein, human
- Inhibitor of Apoptosis Proteins
- NF-kappa B
- Survivin
- X-Linked Inhibitor of Apoptosis Protein
- XIAP protein, human
- Deoxycytidine
- CASP3 protein, human
- CASP9 protein, human
- Caspase 3
- Caspase 9
- Emodin
- Gemcitabine