Emodin sensitizes the gemcitabine-resistant cell line Bxpc-3/Gem to gemcitabine via downregulation of NF-κB and its regulated targets.

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.

• Authors: Wei Zhang, Hui Chen, Dian-Lei Liu, Hong Li, Jiang Luo, Jian-Hong Zhang, Ye Li, Kang-Jie Chen, Hong-Fei Tong, Sheng-Zhang Lin
• Journal: International journal of oncology (Int J Oncol) Vol. 42 Issue 4 Pg. 1189-96 (Apr 2013) ISSN: 1791-2423 [Electronic] Greece
• PMID: 23440366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics, metabolism)
• Antimetabolites, Antineoplastic (pharmacology)
• Apoptosis
• Caspase 3 (genetics, metabolism)
• Caspase 9 (genetics, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Shape (drug effects)
• Deoxycytidine (analogs & derivatives, pharmacology)
• Down-Regulation
• Drug Resistance, Neoplasm (drug effects)
• Drug Synergism
• Emodin (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Inhibitor of Apoptosis Proteins (genetics, metabolism)
• Inhibitory Concentration 50
• NF-kappa B (metabolism)
• Protein Binding
• Survivin
• X-Linked Inhibitor of Apoptosis Protein (genetics, metabolism)
• Gemcitabine