Enhanced chemo-sensitivity by oxidized DHA via inhibiting NF-kB signal pathway

Objective To observe the effects of oxidized DHA and unoxidized DHA on NF-κB signal transduction pathway, and compare its downstream genes, including MMP-2,COX-2 and CyclinD1 expression. Simultaneously, to explore the mechanism of chemo-sensitivity enhancement induced by DHA. Methods Human gastric cell line MGC-803 cells were cultured in vitro with different treatment. Group A was served as control group. The cells in group B, C and D were exposed to 5-FU; Oxidized DHA +5-FU, and unoxidized DHA + 5-FU, respectively. A Luciferase report gene assay was used to detect the NF-κB activation status in these 4 groups. Meanwhile, the mRNA expression of MMP-2, COX-2 and CyclinD1 were detected. Results NF-κB signal transduction pathway was significantly activated in Group B, as compared with that in Group A. In contract, NF-kB signal pathway was found to be inhibited in group C, as cultured with oxidized DHA and 5-FU, with the simultaneously downregulated its downstream genes. Yet, the unoxidized DHA activated the NF-Kb signal pathway and induced chemoresistance. Conclusions Oxidized DHA can enhance the chemo-sensitivity through the inhibition of NF-κB transduction pathway, and might be served as a potential target of chemo-sensitizer.