The Biological Effect And Mechanism Of A Isoflavone Derivative F11 On Breast

The decrease of ovaries function and estrogen in post-menopause women leads to a series clinical syndrome which affect their qualities of life.Many researches reveal that Hormone Replacement Therapy(HRT) could release the peri-menopausl period syndrome,protect Osteoporosis(OP) and cardiovascular disease which were resulted from low level of estrogen in body.However ,long term HRT will produce adverse reactions such as homohemagglutininism,hypertension,dropsy and may increase morbid risks of breast cancer and endometrial cancer.So researchers in the process of seeking to a hormone replacement find phytoestrogen which can release peri-menopausal period syndrome but hasn't adverse reactions.Phytoestrogen(PE) is a heterocycle Polyphenols compounds.the most important of PE is soybean isoflavone(IF) which includes genistein(GEN),daidzein,glycitein.The effect of estrogen on soybean isoflavone has preventive and therapeutical effect on diseases which are connected with the level of estrogen on menopause womam such as high-blood-fat,artherosclerosis(AS),osteoporosis and so on.Epidemiological investigation showed that Southeast Asian especially Japanese who long-term edible soybean the rates of breast cancer , osteoporosis of post-menopause women were lower than that in Europe.Researches showed the main reason is that isoflavone is abundant in the food of Asia women. The structure of isoflavone is similar to estrogen.Isoflavone mainly combineβ-estrogen receptor (ERβ)while poorly combineα-estrogen receptor(ERα)which has no effect on cell proliferation of uterus ,breast and has good effect on anti- osteoporosis,anti-cancer.Its estrogen activity is only 1/1000 of estradiol(E2).It is impossible that meeting the body demand through intaking nature IF dosage.In 1988,Japan Wutian company reconstruct the structure of IF to thrapy OP and achieve good effect in clinic.So reconstructing the structure of isoflavone and remaining its selectivity of estrogen regulation and raising its activity have already become a researching focus on domestic and overseas.In previous studies,we adding different active group to the different parts of GEN struture synthesized a body of isoflavone derivative compounds,of which F11 has better estrogen activity as well as anti-tumor proliferation,anti-OP and prevent cardiovascular disease.The aim of present study is based on this constructing the ovariectomized rat model and culturing HBL-100 to study the biological effect and mechanism of F11 on breast.The results are shown as the following:1.The biological effect on ovariectomized rat breast of F11:Experiment groups:control group,E2 group,F11group,Sham group.Intraperitoneal injection ovariectomized rat with F11 50mg/Kg.d for twelve weeks.It shows that F11 can promote ovariectomized rat vaginal epithelium cells maturity;can ameliorate endometrial tissue atrophy;increase the ratio of uterus wet weight to body weight;can promote rat breast gland augment and make gland cave bigger;increase the level of serum E2 administrated for 4 weeks and decrease normal in 12 weeks;the expression of ERαis weaker than E2 and Sham groups on breast,but the expression of ERβbetter than E2 group,the expression of PCNA is weak.The results show that F11 possess estrogen activity which can promote ovariectomized rat vaginal epithelium cells maturity;can ameliorate endometrial tissue atrophy;can promote rat breast glandular organ hyperplasy ,but is estrogen activity is weaker than E2.It effect of promoting proliferation on breast epithelium cells is weak mainly throuth ERβand bind to it to express estrogen activity.2.The mechanism of F11 on HBL-100:causes a block at G2/M in cell generation cyclecell cycle and induses cells apoptosis; up-regulates the expression of P-JNK, P-P38,down-regulates the expression of P-ERK.It shows that F11 arrest G2/M and induce apoptosis may through activing JNK,P38 and inactivating ERK.