Role of docosahexaenoic acid in enhancement of docetaxel action in patient-derived breast cancer xenografts.

The objective of this study was to investigate if DHA dietary supplementation enhances the anticancer actions of docetaxel (TXT) in two different drug resistant triple negative breast cancer (TNBC) patient-derived xenografts (PDX)s. In two experiments, female NSG mice bearing TNBC PDXs were randomized to one of two nutritionally adequate diets (20% w/w): control (0% DHA), or DHA (3.9% w/w of total fat) and injected with 0 or 5 mg/kg TXT, twice weekly for 6 weeks (n = 8 per group). Treatment response was determined by significant differences in tumor weight, and apoptotic, proliferation and cell cycle markers at endpoint. Mice bearing MAXF574 xenografts fed DHA diet and treated with TXT had a 57% reduction in tumor weight compared to mice fed control diet (P < 0.004), a 64% reduction compared to control + TXT (P < 0.01) and a 34% reduction compared to DHA with no TXT (P < 0.04). DHA + TXT reduced MAXF401 xenografts growth compared to control and control + TXT (by 43% and 34%, respectively, P < 0.05). In both xenografts, DHA + TXT resulted in a higher expression of proapoptotic proteins Ripk1 and Bid, lower expression of proliferation marker Ki67 and anti-apoptotic proteins Bcl-2 and Parp, and a greater increase in cell cycle arrest as measured by decreased Survivin expression when compared to control + TXT mice (P < 0.05). This work is the first to confirm that DHA supplementation during chemotherapy treatment improves TXT action in two PDX models of TNBC. The results suggest that decreases in tumor size occurred via changes in apoptosis, cell proliferation, and cell cycle pathways.