Effects Of Genistein And Chemotherapeutic Agents Combination Treatment On The Growth Of HER-2/neu-overexpressing Human Breast Cancer Cell Line MDA-MB-453 And Its Mechanism

Breast cancer is the first cause of cancer-related deaths among women now. HER-2/neu (c-erbB-2) protein is a member of the epidermal growth factor receptor (EGFR) family and has intrinsic tyrosine kinase activity. Overexpression of HER-2/neu plays an important role in cancer development and progression and has been reported in various malignant tumors. The HER-2 gene is overexpressed in approximately 30% of breast cancer patients, and its overexpression correlates with drug-resistance and a poor prognosis. One of the important factors contributing to the failure of chemotherapy in patients with breast cancer is that the cancer cells become resistant to drug-induced apoptosis. It is reported that HER-2-mediated signal transduction has been implicated in conferring resistance to conventional chemotherapy on cancer cells.Herceptin is a humanized monoclonal anti-HER-2 antibody, which has been reported to have significant therapeutic effects in patients with HER-2/neu-overexpressing breast cancer, particularly when administered in combination with chemotherapy. The major mechanism by which Herceptin exerts its antitumor effects is down-regulation of HER-2/neu. Herceptin has not yet been adopted extensively in the treatment of HER-2-positive breast cancer patients due to the cardiotoxic effects and expensive cost. It is very important to seek the substitute for Herceptin.Genistein(4′,5,7-trihydroxyisoflavone),a natural isoflavone phytoestrogen presented in soybeans,exhibits multiple biological activities resulting in antitumor effects.The traditional Asian diet is rich in soy products may explain in part why the incidence of breast cancer in Asian women is relatively low. Genistein is a potent inhibitor of tyrosine kinase activity, especially that of the epidermal growth factor receptor. Genistein that possesses heterocyclic phenols is similar to the structure of estradiol and acts as estrogen agonist or...