Kenny F S, Gee J M, Nicholson R I, Ellis I O, Morris T M, Watson S A, Bryce R P, Robertson J F
Professorial Unit of Surgery, City Hospital, Nottingham, United Kingdom.
Int J Cancer. 2001 May 1;92(3):342-7. doi: 10.1002/ijc.1213.
Gamma linolenic acid (GLA) possesses a number of selective anti-tumour properties including modulation of steroid receptor structure and function. We have investigated the effect of dietary GLA on the growth, oestrogen receptor (ER) expression and fatty acid profile of ER+ve human breast cancer xenografts. Experimental diets A, B, C, D were commenced after subcutaneous implantation of 40 female nude mice with the MCF-7 B1M cell line (Group A = control diet: B = control diet + GLA supplement: C = control diet + tamoxifen: D = control diet + GLA + tamoxifen; 10 mice/group). The mice were terminated when tumour cross-sectional area reached 250 mm(2). ER H-scores were assessed by immunohistochemical assay and fatty acid profiles by gas-liquid chromatography of termination tumour samples. Groups C and D displayed significantly slower tumour growth (p =.0002, p =.0006) with trend for slower growth in B (p =.065) compared to control Group A. ER was significantly reduced 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 metabolites 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 additive to the reduced ER expression resulting from tamoxifen alone. The effects of GLA on ER function and the possibility of synergistic inhibitory action of GLA with tamoxifen via enhanced down-regulation of the ER pathway require further investigation.
γ-亚麻酸（GLA）具有多种选择性抗肿瘤特性，包括调节类固醇受体的结构和功能。我们研究了饮食中GLA对雌激素受体（ER）阳性人乳腺癌异种移植瘤的生长、ER表达和脂肪酸谱的影响。在用MCF-7 B1M细胞系皮下植入40只雌性裸鼠后，开始给予实验性饮食A、B、C、D（A组 = 对照饮食；B组 = 对照饮食 + GLA补充剂；C组 = 对照饮食 + 他莫昔芬；D组 = 对照饮食 + GLA + 他莫昔芬；每组10只小鼠）。当肿瘤横截面积达到250平方毫米时，处死小鼠。通过免疫组织化学分析评估ER H评分，并通过对处死时肿瘤样本进行气液色谱分析来测定脂肪酸谱。与对照组A相比，C组和D组的肿瘤生长明显较慢（p = 0.0002，p = 0.0006），B组有生长较慢的趋势（p = 0.065）。与A组相比，所有组的ER均显著降低（p < 0.0001），D组（联合治疗）的ER表达明显低于单独使用任何一种治疗的组（p = 0.0002）。接受GLA的两组（B组和D组）肿瘤GLA及其代谢产物水平显著升高（p < 0.0001）。这种ER阳性乳腺癌异种移植模型表明，接受GLA的组中肿瘤ER表达显著降低，这种作用似乎与单独使用他莫昔芬导致的ER表达降低具有相加性。GLA对ER功能的影响以及GLA与他莫昔芬通过增强ER途径的下调而产生协同抑制作用的可能性需要进一步研究。
