Hakkak Reza, Shaaf Saied, Jo Chan Hee, Macleod Stewart, Korourian Soheila
Department of Dietetics and Nutrition, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Oncol Lett. 2011 Jan;2(1):29-36. doi: 10.3892/ol.2010.202. Epub 2010 Nov 8.
Obesity and elevated serum insulin growth factor-1 (IGF-1) level are major risk factors in the development of breast cancer. We investigated the long-term effects of high-isoflavone soy intake and obesity on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumor development and on serum IGF-1 and binding protein (IGFBP-3) levels. Lean and obese female Zucker rats fed casein or high-isoflavone soy protein were orally gavaged at age 50 days with DMBA and sacrificed after 147 days. The majority of lean casein-fed rats (69%) developed mammary tumors compared to 50% in lean soy-fed rats (P=0.176). In the obese groups, 76% of soy-fed rats developed mammary tumors compared to 15% of obese casein-fed rats (P<0.001). At age 43 days, IGFBP-3 was increased in the lean soy-fed rats compared to the lean casein-fed rats (P<0.05). At age 99 days, soy- and obese casein-fed rats exhibited increased serum IGF-1 compared to the lean rats and this increase was maintained for the rest of the experiment (P<0.05). Obese rats fed casein exhibited increased IGFBP-3 levels (P<0.001). However, obese rats fed soy exhibited a significant decrease in IGFBP-3 levels compared to the lean soy-fed rats (P<0.001) and a significant decrease in IGFBP-3 levels compared to the obese casein-fed rats (P<0.001). At age 197 days, IGFBP-3 levels were increased in obese casein-and soy-fed rats (P<0.001). The results suggest that female Zucker rats fed casein diets are protected against DMBA-induced mammary tumors, which is not the case for those on high-isoflavone soy diet, and changes in the concentration of serum IGFBP-3 may contribute to the incidence of DMBA-induced mammary tumors.
肥胖和血清胰岛素样生长因子-1（IGF-1）水平升高是乳腺癌发生的主要危险因素。我们研究了高异黄酮大豆摄入量和肥胖对7,12-二甲基苯并(a)蒽（DMBA）诱导的乳腺肿瘤发生以及血清IGF-1和结合蛋白（IGFBP-3）水平的长期影响。50日龄时，给喂食酪蛋白或高异黄酮大豆蛋白的瘦型和肥胖型雌性 Zucker 大鼠经口灌胃 DMBA，并在147天后处死。与喂食大豆的瘦型大鼠中50%发生乳腺肿瘤相比，大多数喂食酪蛋白的瘦型大鼠（69%）发生了乳腺肿瘤（P = 0.176）。在肥胖组中，76%喂食大豆的大鼠发生了乳腺肿瘤，而喂食酪蛋白的肥胖大鼠中这一比例为15%（P < 0.001）。43日龄时，与喂食酪蛋白的瘦型大鼠相比，喂食大豆的瘦型大鼠的IGFBP-3升高（P < 0.05）。99日龄时，与瘦型大鼠相比，喂食大豆和酪蛋白的肥胖大鼠血清IGF-1升高，且在实验剩余时间内维持这一升高水平（P < 0.05）。喂食酪蛋白的肥胖大鼠IGFBP-3水平升高（P < 0.001）。然而，与喂食大豆的瘦型大鼠相比，喂食大豆的肥胖大鼠IGFBP-3水平显著降低（P < 0.001），与喂食酪蛋白的肥胖大鼠相比也显著降低（P < 0.001）。197日龄时，喂食酪蛋白和大豆的肥胖大鼠的IGFBP-3水平升高（P < 0.001）。结果表明，喂食酪蛋白饮食的雌性 Zucker 大鼠对DMBA诱导的乳腺肿瘤有保护作用，而高异黄酮大豆饮食的大鼠则不然，血清IGFBP-3浓度的变化可能与DMBA诱导的乳腺肿瘤发生率有关。
