Effect of dietary GLA plus /-tamoxifen on the growth, ER expression and fatty acid profile of ER positive human breast cancer xenografts

Gamma linolenic acid (GLA) possesses a number of selective anti-tumour prop erties including modulation of steroid receptor structure and function. We have investigated the effect of dietary GLA on the growth, oestrogen recept or (ER) expression and fatty acid profile of ER+ve human breast cancer xeno grafts, Experimental diets A, B, C, D were commenced after subcutaneous imp lantation of 40 female nude mice with the MCF-7 BIM cell line (Group A = co ntrol diet: B = control diet + GLA supplement: C = control diet + tamoxifen : D = control diet + GLA + tamoxifen; 10 mice/group). The mice were termina ted when tumour cross-sectional area reached 250 mm(2). ER H-scores were as sessed by immunohistochemical assay and fatty acid profiles by gas-liquid c hromatography of termination tumour samples. Groups C and D displayed signi ficantly slower tumour growth (P = .0002, P = .0006) with trend for slower growth in B (p = .065) compared to control Group A. ER was significantly re duced in all groups compared to A (p < .0001)with Group D (combined therapy ) displaying markedly lower ER expression than with either therapy alone (p = .0002), There were significantly raised levels of tumour GLA and metabol ites in the two groups (B and D) receiving GLA (p < .0001), This xenograft model of ER+ve breast cancer has demonstrated significantly lower tumour ER expression in those groups receiving GLA, an effect which appears to be ad ditive to the reduced ER expression resulting from tamoxifen alone. The eff ects of GLA on ER function and the possibility of synergistic inhibitory ac tion of GLA with tamoxifen via enhanced down-regulation of the ER pathway r equire further investigation. (C) 2001 Wiley-Liss, Inc.