Effects of Omegaven®, EPA, DHA and oxaliplatin on oesophageal adenocarcinoma cell lines growth, cytokine and cell signal biomarkers expression

Abstract

Background: There is limited evidence assessing the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oesophageal adenocarcinoma, both in vitro and in vivo. We evaluated the effects of the omega-3 PUFA and oxaliplatin on OE33 and OE19 cells.

Method: The two oesophageal cells were treated with Omegaven® (fish oil emulsion), EPA, DHA and oxaliplatin and incubated for up to 144 h.

Results: The following inhibitory effects were observed on OE33 cells: EPA reduced cell growth by 39% (p = 0.001), DHA by 59% (p < 0.000) and Oxaliplatin by 77% (p < 0.000). For OE19 cells, the EPA reduced growth by 1% (p = 0.992), DHA by 26% (p = 0.019) and oxaliplatin by 76% (p < 0.000). For both cells, Omegaven® resulted in reduced cell growth at intermediate concentrations (20-40 μM) and increased cell growth at low (10 μM) and high (50 μM) concentrations. DHA, Omegaven® and oxaliplatin were associated with significant downregulation of VEGF and p53 protein, and upregulation of p21 protein. DHA, Omegaven® and Oxaliplatin also led to significant downregulation of the total ERK1/2 and Akt proteins.

Conclusion: DHA, Omegaven® and oxaliplatin were associated with downregulation of p53 and VEGF in both cells. Of the PUFAs studied, DHA alone or in combination (Omegaven®) had greater in vitro anti-cancer effects than EPA alone.

Fig. 1

Effects of EPA, DHA, Omegaven® and oxaliplatin treatments over time on VEGF expression in (a) OE33 and (b) OE19 cells. Analysis was made using ELISA assays in duplicate. The graphs represent the mean and standard deviation (SD) of VEGF concentration (pg/mL) expressed as a percentage of control. Statistical analyses was by two tailed student’s t test of log 10 transformed data, and a P value of <0.05 considered significant

Fig. 2

Effects of EPA, DHA, Omegaven® and oxaliplatin treatments over time on p53 (top panel) and p21 (bottom panel) expression in OE33 cells. Analysis was made using ELISA assays in duplicate. The graphs represent the mean and standard deviation (SD) of p53 and p21 proteins (percentage of control). Using two tailed student’s t test of log 10 transformed data and P value of <0.05 considered significant

Fig. 3

Effects of EPA, DHA, Omegaven® and oxaliplatin treatments over time on p53 (top panel) and p21 (bottom panel) expression in OE19 cells. Analysis was made using ELISA assays in duplicate. The graphs represent the mean and standard deviation (SD) of p53 and p21 proteins (percentage of control). Using two tailed student’s t test of log 10 transformed data and P value of <0.05 considered significant

Fig. 4

Effects of EPA, DHA, Omegaven® and oxaliplatin treatments over time on akt expression in OE33 (a) and OE19 (b) cells. Analysis was made using ELISA assays in duplicate. The graphs represent the mean and standard deviation (SD) of akt (percentage of control). Using two tailed student’s t test of log 10 transformed data and P value of <0.05 considered significant. The OE19 cell lines akt expression data (Control) for omegaven® treatment was not read during ELISA assay (technical issues), hence not presented

Fig. 5

Effects of EPA, DHA, Omegaven® and oxaliplatin treatments over time on ERK 1/2 expression in OE33 (a) and OE19 (b) cells. Analysis was made using ELISA assays in duplicate. The graphs represent the mean and standard deviation (SD) ERK 1/2 (percentage of control). Using two tailed student’s t test of log 10 transformed data and P value of <0.05 considered significant