Anticancer Activity of Fish Oils Against Human Lung Cancer Is Associated With Changes in Formation of PGE(2) and PGE(3) and Alteration of Akt Phosphorylation

作者：Yang Peiying^*; Cartwright Carrie; Chan Diana; Ding Jibin; Felix Edward; Pan Yong; Pang Jihai; Rhea Patrea; Block Keith; Fischer Susan M; Newman Robert A

来源：Molecular Carcinogenesis, 2014, 53(7): 566-577.

DOI：10.1002/mc.22008

• antiproliferative activity
• NSCLC cells
• fish oil EPA
• COX-2
• prostaglandins

The beneficial effects of omega-3 fatty acids are believed to be due in part to selective alteration of arachidonate metabolism that involves cyclooxygenase (COX) enzymes. Here we investigated the effect of eicosapentaenoic acid (EPA) on the proliferation of human non-small cell lung cancer A549 (COX-2 over-expressing) and H1299 (COX-2 null) cells as well as their xenograft models. While EPA inhibited 50% of proliferation of A549 cells at 6.05 mu M, almost 80 mu M of EPA was needed to reach similar levels of inhibition of H1299 cells. The formation of prostaglandin (PG)E-3 in A549 cells was almost threefold higher than that of H1299 cells when these cells were treated with EPA (25 mu M). Intriguingly, when COX-2 expression was reduced by siRNA or shRNA in A549 cells, the antiproliferative activity of EPA was reduced substantially compared to that of control siRNA or shRNA transfected A549 cells. In line with this, dietary menhaden oil significantly inhibited the growth of A549 tumors by reducing tumor weight by 58.8 +/- 7.4%. In contrast, a similar diet did not suppress the development of H1299 xenograft. Interestingly, the ratio of PGE(3) to PGE(2) in A549 was about 0.16 versus only 0.06 in H1299 xenograft tissues. Furthermore, PGE(2) up-regulated expression of pAkt, whereas PGE(3) downregulated expression of pAkt in A549 cells. Taken together, the results of our study suggest that the ability of EPA to generate PGE(3) through the COX-2 enzyme might be critical for EPA-mediated tumor growth inhibition which is at least partly due to down-regulation of Akt phosphorylation by PGE(3).

• 出版日期2014-7