Objective To explore the mechanisms by which genistein and daidzein inhibit the growth of prostate cancer cells. Methods LNCaP and PC-3 cells were exposed to genistein and daldzein and cell viability was determined by...Objective To explore the mechanisms by which genistein and daidzein inhibit the growth of prostate cancer cells. Methods LNCaP and PC-3 cells were exposed to genistein and daldzein and cell viability was determined by MTF assay and cytotoxicity of the drugs by LDH test. Flow cytometry (FCM) was used to assess the cell cycle in LNCaP and PC-3 cells. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to examine the expression of PTEN gene (a tumor suppressor gene), estrogen receptor alpha gene (ERα), estrogen receptor beta gene (ERβ), androgen receptor gene (AR) and vascular endothelial growth factor gene (VEGF). Results The viability of PC-3 and LNCaP cells decreased with increasing concentrations and exposure time of genistein and daidzein. Genistein increased G2/M phase cells in PC 3 cells while decreased S phase cells in LNCaP cells in a dose-dependent manner. Daidzein exerted no influence on the cell cycle of LNCaP and PC-3 cells, but the apoptosis percentage of LNCaP cells was elevated significantly by daidzein, Genistein induced the expression of PTEN gene in PC-3 and LNCaP cells. Daidzein induced the expression of PTEN gene in LNCaP but not in PC-3 cells. The expression of VEGF, ERα and ERβ genes decreased and AR gene was not expressed after incubation with genistein and daldzein in PC-3 cells. In LNCaP cells, the expression of VEGF and AR gene decreased but there was no change in the expression of ERα and ERβ gene after incubation with genistein and daidzein. Conclusion Genistein and daidzein exert a timeand dose-dependent inhibitory effect on PC-3 and LNCaP cells. The down-regulation of ER gene by daidzein influences the growth of PC-3 ceils directly, The inhibition of PC-3 cells by genistein and that of LNCaP cells by genistein and daidzein may be via Alct pathway that is repressed by PTEN gene, which subsequently down-regulates the expression of AR and VEGF genes. Our results suggest that the expression of PTEN gene plays a key role and several pathway展开更多
基金This work was supported by the National 973 Program of China "Investigation the Protective Effects of Important Responsive Proteinsin the Damage Cells Caused by Environmental Chemical Pollutants"
文摘Objective To explore the mechanisms by which genistein and daidzein inhibit the growth of prostate cancer cells. Methods LNCaP and PC-3 cells were exposed to genistein and daldzein and cell viability was determined by MTF assay and cytotoxicity of the drugs by LDH test. Flow cytometry (FCM) was used to assess the cell cycle in LNCaP and PC-3 cells. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to examine the expression of PTEN gene (a tumor suppressor gene), estrogen receptor alpha gene (ERα), estrogen receptor beta gene (ERβ), androgen receptor gene (AR) and vascular endothelial growth factor gene (VEGF). Results The viability of PC-3 and LNCaP cells decreased with increasing concentrations and exposure time of genistein and daidzein. Genistein increased G2/M phase cells in PC 3 cells while decreased S phase cells in LNCaP cells in a dose-dependent manner. Daidzein exerted no influence on the cell cycle of LNCaP and PC-3 cells, but the apoptosis percentage of LNCaP cells was elevated significantly by daidzein, Genistein induced the expression of PTEN gene in PC-3 and LNCaP cells. Daidzein induced the expression of PTEN gene in LNCaP but not in PC-3 cells. The expression of VEGF, ERα and ERβ genes decreased and AR gene was not expressed after incubation with genistein and daldzein in PC-3 cells. In LNCaP cells, the expression of VEGF and AR gene decreased but there was no change in the expression of ERα and ERβ gene after incubation with genistein and daidzein. Conclusion Genistein and daidzein exert a timeand dose-dependent inhibitory effect on PC-3 and LNCaP cells. The down-regulation of ER gene by daidzein influences the growth of PC-3 ceils directly, The inhibition of PC-3 cells by genistein and that of LNCaP cells by genistein and daidzein may be via Alct pathway that is repressed by PTEN gene, which subsequently down-regulates the expression of AR and VEGF genes. Our results suggest that the expression of PTEN gene plays a key role and several pathway