Studies on inhibitory effects of isoflavones on endometrial carcinogenesis.

近年来，子宫内膜癌在日本和西方国家的发病率呈上升趋势。流行病学研究表明，食用含有大豆和大豆制品的饮食可以降低患子宫内膜癌的风险。然而，异黄酮对子宫内膜癌变的影响尚未见报道。因此，我们试图探讨染料木素和didzein是否对小鼠子宫内膜癌变有抑制作用。短期实验：单次给予染料木素（1 mg/30 g bw）显著降低E2 （5 ppm）诱导的卵巢切除小鼠子宫c-jun、IL-1α和TNF-a mrna的表达水平（P<0.005、P<0.05和P<0.01）。大豆苷元显著抑制e2诱导的c-fos和IL-1α的表达（P<0.01）。长期实验（30周）：140只雌性ICR小鼠左、右子宫分别灌胃含n -甲基-n -亚硝基脲溶液（1 mg/100 g bw）和生理盐水（对照组）。他们被分成六组；组1单独给予E2 （5ppm）。组2给予E2和染料木素（1 mg/30 g bw, s.c，每4周）。第3组暴露于E2和大豆苷元（1 mg/30 g bw, s.c，每4周）。第4组和第5组分别饲喂染料木素和大豆苷元，继续饲喂基础饲粮。第6组继续饲喂基础日粮，作为对照组。实验结束时，E2联合染料木素或大豆苷元组子宫内膜腺癌和不典型增生的发生率均显著低于单独E2组（P<0.01和P<0.05）。提示gensitin和大豆苷元对e2相关的小鼠子宫内膜癌变均有抑制作用，可能是通过抑制c-fos/jun、IL-1α和TNF-α来实现的。

Recently, the incidence of endometrial carcinoma has been increasing in Japan as well as in the Western countries. Epidemiological studies gave suggested that consumption of diets containing soybeans and soy-based products reduce the risk of endometrial cancers. However, the effects of isoflavones on endometrial carcinogenesis have not been reported. Thus, we have attempted to address whether genistein and didzein exert suppressive effects on mouse endometrial carcinogenesis.Short-term experiment : Single s.c. administration of genistein (1 mg/30 g bw) significantly decreased the levels of E2 (5 ppm)-induced expression of c-jun, IL-1α and TNF-a mRNAs in the uteri of ovarectomized mice (P<0.005, P<0.05 and P<0.01, respectively). Daidzein significantly inhibited E2-induced expression of c-fos and IL-1α (P<0.01).Long-term experiment (30 weeks) : 140 female ICR mice were given N-methyl-N-nitrosourea containing solution (1 mg/100 g bw) and normal saline (as controls) into the left and right uterine corpora, respectively. They were divided into six groups ; group 1 was given E2 (5 ppm) alone. Group 2 was given E2 and genistein (1 mg/30 g bw, s.c., every 4 weeks). Group 3 was exposed to E2 and daidzein (1 mg/30 g bw, s.c., every 4 weeks). Groups 4 and 5 respectively received genistein and daidzein, and were kept on the basal diet. Group 6 was kept on the basal diet and served as a control. At the termination of the experiment, incidences of endometrial adenocarcinoma and atypical hyperplasia of the group given E2 and genistein or daidzein were significantly lower than the group given E2 alone (P<0.01 and P<0.05, respectively). It is suggested that both gensitein and daidzein have an inhibitory effect on E2-realted endometrial carcinogenesis in mice, possibly by suppression of c-fos/jun, IL-1α and TNF-α.