Studies on inhibitory effects of isoflavones on endometrial carcinogenesis.

异黄酮对子宫内膜癌抑制作用的研究。

基本信息

批准号：
12671588
负责人：
NIWA Kenji
金额：
$ 1.22万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671588/
关键词：
Isoflavones Endometrium Chemoprevention Estroqens c-fos jun IL-1α TNF-α Mice 発癌抑制ゲニステインダイゼイン

项目摘要

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.

最近，日本和西方国家的子宫内膜癌事件一直在增加。流行病学研究表明，食用含有大豆和大豆产品的饮食量降低了子宫内膜癌的风险。但是，异黄酮对子宫内膜癌发生的影响尚未报道。这是我们试图解决染料木黄酮和狄兹因是否对小鼠子宫内膜致癌作用抑制作用。SHORT-TIME实验：Single S.C.染料木黄酮（1 mg/30 g BW）的给药显着降低了卵巢切除小鼠子宫中C-JUN，IL-1α和TNF-A mRNA的E2（5 ppm）诱导的水平（P <0.005，P <0.05，P <0.05和P <0.01）。 Daidzein显着抑制了E2诱导的C-FOS和IL-1α的表达（P <0.01）。长期实验（30周）：从左右的Uterine Corpora中，给予含有N-甲基N-硝基溶液（1 mg/100 g BW）的N-甲基-N-硝基库（1 mg/100 g BW）和正常的盐水（作为对照）。他们分为六组；仅给第1组E2（5 ppm）。将第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Daidzein（每4周，1 mg/30 g BW，S.C。）。第4组和第5组分别接受了染料木黄酮和大泽蛋白，并以基本饮食为基础。第6组保留在基本饮食中，并作为对照。在实验终止时，给定的E2和Genastein或Daidzein组的子宫内膜腺癌和非典型增生的发生率显着低于单独给定的E2组（分别为P <0.01和P <0.05）。据建议，生长素和大二氮素对小鼠的E2造成的子宫内膜致癌作用都有抑制作用，这可能是通过抑制C-FOS/JUN，IL-1α和TNF-α的抑制作用。