Emodin potentiates the antitumor effects of gemcitabine in PANC-1 pancreatic cancer xenograft model in vivo via inhibition of inhibitors of apoptosis.

Abstract

Pancreatic cancer is a highly aggressive malignant disease. Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. As members of apoptosis inhibitors, Survivin and XIAP play an important role in chemotherapy resistance in pancreatic cancer. Emodin has therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and emodin enhanced antitumor efficacy in pancreatic cancer. The application of the combination therapy triggered significantly higher frequency of pancreatic cancer cell apoptosis. Our research demonstrated that the combination of emodin and gemcitabine resulted in significantly reduced tumor volumes compared to gemcitabine or emodin treatment alone. Immunohistochemistry and western immunoblot analyses showed that Survivin and XIAP expression were downregulated in emodin and the combination groups compared to the other two groups. Reverse transcriptase polymerase chain reaction analyses showed that Survivin and XIAP mRNA expression in emodin and the combination groups were downregulated significantly compared to the other two groups. Furthermore, the expression of the nuclear transcription factor κB (NF-κB) protein and NF-κB mRNA were downregulated in the emodin and the combination groups. DNA-binding activity of NF-κB was inhibited in emodin and combination groups compared to the other groups. This study suggests that emodin potentiates the antitumor effects of gemcitabine in PANC-1 cell xenografts via promotion of apoptosis and IAP suppression.

• Authors: Hong-Chun Guo, He-Qi Bu, Jiang Luo, Wei-Tian Wei, Dian-Lei Liu, Hui Chen, Hong-Fei Tong, Zhao-Hong Wang, Hua-Yong Wu, Hong-Hai Li, Ming-Ming Zuo, Wei Li, Sheng-Zhang Lin
• Journal: International journal of oncology (Int J Oncol) Vol. 40 Issue 6 Pg. 1849-57 (Jun 2012) ISSN: 1791-2423 [Electronic] Greece
• PMID: 22378302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• BIRC5 protein, human
• Inhibitor of Apoptosis Proteins
• Ki-67 Antigen
• NF-kappa B
• Survivin
• X-Linked Inhibitor of Apoptosis Protein
• XIAP protein, human
• Deoxycytidine
• Caspases
• Emodin
• Gemcitabine

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (antagonists & inhibitors)
• Caspases (metabolism)
• Cell Line, Tumor
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Down-Regulation
• Drug Synergism
• Emodin (administration & dosage)
• Humans
• Inhibitor of Apoptosis Proteins (genetics, metabolism)
• Ki-67 Antigen (metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• NF-kappa B (antagonists & inhibitors, metabolism)
• Pancreatic Neoplasms (drug therapy, pathology)
• Survivin
• Tumor Burden (drug effects)
• X-Linked Inhibitor of Apoptosis Protein (genetics, metabolism)
• Xenograft Model Antitumor Assays
• Gemcitabine