The Effects Of Dietary Genistein On Breast Cancer Chemotherapy

Currently,breast cancer is ranked as one of the leading causes of female.Sensitivity of breast cancer to chemotherapy defines its’ prognosis and recurrence.Therefore,studies in breast cancer’s sensitivity to chemotherapy aroused increasing concerns.Genistein is a typical phytoestrogen which is abundant in daily diet.It binds to estrogen receptor and agonist ER-dependent pathway,because of its structural similarity to estrogen.Since breast cancer is an estrogen-sensitive tumor,it’s development and prognosis may also be interfered with the dietary intake of genistein.However,up to now,the researches on genistein and breast cancer’s sensitivity to chemotherapy are rare and are mainly at cellular level.The present work was engaged in investigating the impact of dietary genistein intake on anti-tumor effects of chemotherapy in both animal breast cancer model and clinical cases.The main contents of this work are as follows:1.We observed the dietary genistein’s effects on cisplatin anti-tumor effect in a breast cancer xenograft mice model.To get ride of the interfere of endogenous estrogen,and to mimic postmenopausal breast cancer patients’ physiological situation,ovariectomy was applied in mice model.The nude mice weregavaged with 0,5,25,and 45 mg/kg-bw genistein to investigate the effect of genistein on the chemotherapy effect of cisplatin(3 mg/kg-bw)in breast cancer.The growth of xenograft tumor was observed daily.And the contents of genistein metabolites in tumor tissue,liver tissue and plasma were analyzed via LC-MS/MS.The expression of Ki67 in breast tumors was examined by immunohistochemical staining.The apoptosis of breast cancer cells was detected by TUNEL staining.2.We investigated the distribution of genistein metabolites in normal breast tissue,para-carcinoma tissues and tumor tissues of breast cancer patients via LC-MS/MS.And the proliferation potential of breast cancer tumor after chemotherarpy was evaluated via Ki67 expression level in breast tumor tissues so that the effect of dietary genistein exposure on the chemotherapy efficiency was analyzed.3.Neoadjuvant chemotherapy patients were targeted.We collected their morning the fasting urine sample were collected from patients to detect the genistein metabolites urine excretion via LC-MS/MS,fancilitate assessment of dietary genistein exposure during chemotherapy.According to RECIST tumor chemotherapy efficiency evaluation method,based on the imaging data of breast cancer tumors before/after chemotherapy,the targeted patients’ chemotherapy efficiency were obtained,the correlation between genistein urinary excretion and chemotherapy efficiency were analyzed.The main results and conclusions were obtained as follows:1.At 5mg/kg.d genistein antagonized cislpatin’s anti-tumor effects in ovariectomized MCF-7 xenograft model.While at dosage of 25-45 mg/kg.d,genistein’s negative effect was not significant.2.The contents of total genistein metabolites in normal tissues,para-carcinoma tissue,and tumor tissues of breast cancer patients were 0.0236±0.070 nmol/g,0.0330±0.0334 nmol/g,and 0.0372±0.0350 nmol/g,respectively.3.Logistic regression analysis showed that high levels of genistein in breast tumour tissues significantly increased the expression of Ki67(p=0.013),genistein in breast tumor tissue can enhances the proliferation of cancer cell,result an adverse effect on the efficacy of chemotherapy for breast cancer.Therefore,tumor tissue genistein exposure is a potential risk factor for the effect of chemotherapy.4.The average urinary genistein concentration in neoadjuvant chemotherapy breast cancer patients was 0.0719±0.0663 nmol/mL.The urinary genistein level in patients undergoing neoadjuvant chemotherapy had no significant effect on the growing of tumors during chemotherapy(p>0.05)via ordinal logistic regression analysis,that is to say genistein showed no effect on the efficacy of chemotherapy.In sum,genistein dietary exposure showed dose-dependent effect on the efficiency of chemotherapy in breast cancer at the animal experimental level,and a negative effect of chemotherapy is produced by low-dose genistein.In clinical studies,for different chemotherapy methods,genistein exposure has different effects on the efficiency of chemotherapy,and the presence of genistein in breast tumor tissue showed a bad chemotherapy effects for breast cancer patient;while urinary genistein exposure showed no significant effect on the efficacy of neoadjuvant chemotherapy.Therefore,dietary genistein exposure may affect the efficiency of breast cancer chemotherapy.