Reversal Effect of Docosahexaenoic Acid on Taxol Resistance in Human Ovarian Carcinoma A2780/T Cells

Docosahexaenoic Acid (DHA), a member of n-3 PUFAs, has been reported to have multiple beneficial anticancer actions. However, not much was known about the role in ovarian cancer. The aim of this study was to assess the effects of DHA on reversing drug resistance and explore the possible mechanisms in ovarian cancer. The results showed that DHA dramatically enhanced the sensitivity of cells to Taxol in A2780/T cells rather than A2780. Additionally, Taxol and DHA in combination could alter the cell cycle distribution and arrest the cell cycle in G0/G1 phase. We also found that DHA promoted the chemotherapeutic drug accumulation in cells and inhibited the expression of P-gp and other MDR related proteins, including BRCP, MRP and LRP. The activation of NF-κB and phosphorylation of P38MAPK were found markedly inhibited by pretreated DHA. To summarize, DHA could reverse Taxol resistance by inhibiting expression of P-gp and other MDR related proteins, as well as blocking NF-KB and p38MAPK pathways. DHA, a natural agent, might be widely used as a supplemented method in fighting against cancer in future.