Adiponectin modulates DCA-induced inflammation via the ROS/NF-κ B signaling pathway in esophageal adenocarcinoma cells.

Abstract

BACKGROUND:

Deoxycholic acid (DCA) promotes the development and progression of esophageal adenocarcinoma (EAC) by inducing inflammation. Adiponectin is reported to have anti-inflammatory and anti-tumor effects.

PURPOSE:

This study investigated the effects of two types of adiponectin, full-length adiponectin (f-Ad) and globular adiponectin (g-Ad), on DCA-induced inflammation, and investigated the involvement of the reactive oxygen species (ROS)/NF-κB signaling pathway in inflammation in EAC.

METHODS:

OE19 cells were treated with DCA (50-300 μM) and/or f-Ad/g-Ad (10.0 μg/ml) or N-acetylcysteine (NAC). The viability of cells exposed to DCA was measured by use of the MTT assay. mRNA and protein levels of the inflammatory factors were examined by real-time PCR and ELISA. Intra-cellular ROS levels were determined by use of flow cytometry. Protein levels of total and p-NF-κB p65 were measured by western blot.

RESULTS:

DCA induced dose and time-dependent cytotoxicity. mRNA and protein expression of TNF-α, IL-8, and IL-6 in cells treated with DCA alone were up-regulated, and intra-cellular ROS and p-NF-κB p65 protein levels were also increased. g-Ad promoted inflammatory factor production, ROS levels, and p-NF-κB p65 protein expression whereas f-Ad had a suppressive effect. When combined with DCA, g-Ad enhanced the pro-inflammatory effect of DCA whereas f-Ad, similar to NAC, suppressed the effect.

CONCLUSION:

DCA has a pro-inflammatory effect in EAC. f-Ad has an anti-inflammatory effect whereas g-Ad seems to have a pro-inflammatory effect in an ROS/NF-κB p65-dependent manner. This indicates that f-Ad could be a potential anti-inflammatory reagent for cancer therapy.

• Authors: Rong Zhang, Xiaoran Yin, Haitao Shi, Jie Wu, Pramod Shakya, Dong Liu, Jun Zhang
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 59 Issue 1 Pg. 89-97 (Jan 2014) ISSN: 1573-2568 [Electronic] United States
• PMID: 24096876 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adiponectin
• Reactive Oxygen Species
• Transcription Factor RelA
• Deoxycholic Acid

Topics

• Adenocarcinoma (chemistry, drug therapy, prevention & control)
• Adiponectin (physiology, therapeutic use)
• Cell Line, Tumor
• Deoxycholic Acid
• Disease Progression
• Drug Evaluation, Preclinical
• Esophageal Neoplasms (chemistry, drug therapy, prevention & control)
• Humans
• Inflammation (metabolism, prevention & control)
• Reactive Oxygen Species (metabolism)
• Signal Transduction (physiology)
• Transcription Factor RelA (physiology)