Studies on inhibitory effects of isoflavones on endometrial carcinogenesis.

近年来，子宫内膜癌的发病率在日本和西方国家都在增加。流行病学研究表明，食用含有大豆和大豆制品的饮食可降低患子宫内膜癌的风险。然而，对子宫内膜癌发生的影响，还没有报道。因此，我们试图解决染料木黄酮和didzein是否发挥抑制小鼠子宫内膜癌的发生。给予染料木黄酮（1 mg/30 g bw）显著降低E2（5 ppm）诱导的卵巢切除小鼠子宫中c-jun、IL-1α和TNF-α mRNA的表达水平（分别为P<0.005、P<0.05和P<0.01）。长期实验（30周）：140只雌性ICR小鼠，分别于左、右子宫体内注射含N-甲基-N-亚硝基脲溶液（1 mg/100 g bw）和生理盐水（对照组）。他们被分为六组;第一组仅给予E2（5 ppm）。第2组给予E2和染料木黄酮（1 mg/30 g bw，s.c.，每4周）。第3组暴露于E2和大豆黄酮（1 mg/30 g bw，s.c.，每4周）。第4组和第5组分别添加染料木素和大豆黄酮，并保持基础日粮。第6组为对照组，饲喂基础日粮。实验结束时，E2联合染料木素或大豆黄酮组子宫内膜腺癌和不典型增生的发生率均显著低于E2组（P<0.01和P<0.05）。提示染料木素和大豆苷元对E2诱导的小鼠子宫内膜癌的发生有抑制作用，其机制可能与抑制c-fos/jun、IL-1α和TNF-α有关。

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.