Abstract: Synergistic Action of Genistein and TRAIL in Inducing Apoptosis of Human Breast CancerMCF-7 CellsJingjie ZHAO1, BaotingWANG1, Guowei HUANG1, Jihui HAO2, Lingzhang MENG3, Ming YU1Correspondence to: Ming YU, E-mail: minnieyu@tijmu.edu.cn1Department of Nutriology and Food Hygiene, Tianjin Medical University School of Public Health, Tianjin 300070, China2Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China3Reference Laboratory of National Center forAIDS/STD Control and Prevention, China Center for Diseases Control, Beijing 102206, ChinaThis work was supported by National Natural Science Foundation of China (No. 30701013); Funds of Tianjin Education Committee forScientific Development of Colleges and Universities (No. 20060210)Abstract Objective: To investigate the synergistic action and the potential internal mechanism of Genistein ( Gen ) combinedwith Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand ( TRAIL ) in proliferation and apoptosis of breast cancer cell lineMCF-7. Methods: MCF-7 cells were treated with Gen at doses of 1.25, 2.5, 5, 10, 20 and 40μg/mL and with TRAIL of 1, 10, 100 and1000 ng/mL, respectively. Cell proliferation was determined by MTT assay. Based on the results of MTT, Gen ( 20 μg/mL ) and TRAIL( 100ng/mL ) were administered for the follow-up tests. The MCF-7 cells were then divided into four groups: the control group, Gen ( fi-nal concentration: 20 μg/mL ) group, TRAIL ( final concentration: 100n g/mL ) group, and the combination group. After different treat-ment, apoptosis of MCF-7 cells was detected by flow cytometry ( FCM ). Caspase-3 activity was measured by immunofluorescence.And the expression of NF-κB was detected by enzyme-linked immunosorbent assay ( ELISA ). Results: TRAIL-inhibited proliferationand TRAIL-induced apoptosis in MCF-7 cells were promoted by the combined use of Gen. The inhibition ratio reached 63.78% ±2.61% and apoptotic rate was increased to 42.20% ± 1.35%, significantly higher than thoese in the group treated with TRAIL alome (P < 0.01 ). In addition, compared with TRAIL-treated cells, cells treated with Gen and TRAIL showed enhanced caspase-3 activity (44.000 ± 0.445 μmol/L ). The content of NF-κB ( 177.453 ± 25.389 pg/mL ) was significantly lower in the group treated with the combi-nation therapy than in the group treated with TRAIL alone ( 343.333 ± 8.064 pg/mL ) ( P < 0.01 ). Conclusion: Gen can synergizeTRAIL to inhibit cell proliferation and induce apoptosis, thus increasing the sensitivity of TRAIL in MCF-7 cells. The mechanismmight be that Gen has a synergistic action with TRAIL to activate caspase-3 and in-hibit the formation of NF-κB, resulting in the apoptosis of MCF-7 cells.Keywords Genistein; TRAIL; Apoptosis; Induction; Breast cancer MCF-7 cell