Genistein On Tumor Effect Of Human Breast Cancer Cells And Hematopoietic Radiation Protective Role In Experimental Research

In recent years, genistein has attracted considerable attention because epidemiologic studies showed that consumption of soybean- containing diets was associated with a low incidence of certain human cancers in Asia populations.Several possible mechanisms for the anticancer effects of genistein have been proposed,including inhibition of protein tyrosine kinase activity,topoisomeras II inhibition,induction of differentiation,and inhibition of angiogenesis. It has also been shown that genistein inhibits cell proliferation, exerts a specific G2-M arrest and induces cell apoptosis. In this study we investigated the cell growth inhibition effects and hematology irradiation protective effects of genistein, integrating with radiotherapy, through cell culture and establishment of heterologous graft model of human breast cancer in nude mice. The aim of our studies was to provide experimental fundaments for the potential clinical use of genistein. Methods: Firstly, to evaluate the selective cell proliferation inhibitive effects of genistein on different cells,the IC50 values of MCF ?7,MDA ?MB ?3 1, IEC ?6,CFU ?F and CFU ?GM in the use of genistein were measured using MTT and colony forming assay. Furthermore, we used flow cytometry cell cycle, 3H ?TdR to investigate if integrating of genistein with 60Co i radiotherapy has accumulative effects on cultured MCF?, and further explored its possible molecule mechanisms. Secondly, mices were treated with radiation and genistein to investigate the hematology irradiation protective effects of genistein. Thirdly, heterologous graft models of human breast cancer in nude mice were established. The inhibition of tumor growth and the hematology irradiation protective effects of genistein integrating with ionizing radiation were studied simultaneously using immunohistochemistry and image analysis. Furthermore, several main factors of curative effects were analysised to find an optimism treatment to form experimental fundament for the potential clinical use of genistein. Results: 1. The selective 鑕ll proliferation inhibitive effects of genistein on different cells were as follows:MDA ?MB ?31 > MCF ?> IEC ?> CFU ?GM > CFU ?F.It suggests that genistein has a higher cell proliferation inhibitive effect on tumor cells and may be an effective anti- cancer drug with very low toxicity. 2. Both Genistein(20?100 ii M) and 60Co i irradiation(l8Gy) has cell proliferation inhibitive effect and can inhibit DNA synthesization. Comparing with other groups, the group treating with genistein after 60Co ~? irradiation showed significantly tumor growth inhibition.These results indicated that genistein using after irradiation may have cooperative effects with 60Co i radiotherapy. Furthermore,our flow cytometry results suggested that effects of G2-M arrest and cell apoptosis induced by genistein using after irradiation were much higher and it may be one of its possible molecule mechanisms. 3. Genistein (2.0 ?16.0mg/kg) sub-cutaneous administrating before irradiation(60Co,2 . OGy) have hematology irradiation protective effect and 3. Genistein (2.0 ?16.0mg/kg) sub-cutaneous administrating before irradiation(60Co ,2 . OGy) have hematology irradiation protective effect and show significantly dose-dependent effect in the range of 2.0?.0mg/kg. Our results...