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Adiponectin Modulates DCA-Induced Inflammation via the ROS/NF-Kappa B Signaling Pathway in Esophageal Adenocarcinoma Cells

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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.

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Acknowledgments

This work was supported by the Important Clinic Project of the Chinese Ministry of Health (no. 2007353). This work was supported by the Office of Oncology Research (Zong-Fang Li). We thank Dr Guleng B for his excellent technical assistance.

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Correspondence to Jun Zhang.

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Zhang, R., Yin, X., Shi, H. et al. Adiponectin Modulates DCA-Induced Inflammation via the ROS/NF-Kappa B Signaling Pathway in Esophageal Adenocarcinoma Cells. Dig Dis Sci 59, 89–97 (2014). https://doi.org/10.1007/s10620-013-2877-5

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  • DOI: https://doi.org/10.1007/s10620-013-2877-5

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