response of mouse breast cancer cells to anastrozole, tamoxifen, and the combination阿那曲唑小鼠乳腺癌细胞的反应,它莫西芬,组合.pdfVIP

Journal of Biomedicine and Biotechnology • 2005:1 (2005) 10–19 • DOI: 10.1155/JBB.2005.10 RESEARCH ARTICLE Response of Mouse Breast Cancer Cells to Anastrozole, Tamoxifen, and the Combination J. M. Xanthopoulos, A. E. Romano, and S. K. Majumdar∗ Department of Biology, Lafayette College, Easton, PA 18042-1778, USA Received 17 May 2004; accepted 23 August 2004 The murine breast cancer cells (4T1) grown both in female BALB/c mice and in culture were treated with anastrozole (50 µg/mL), tamoxifen citrate (5 µg/mL), and the combination of the two drugs in order to determine treatment efficacies, toxic potential, and the mechanism of cell death. The in vivo treatments were evaluated by monitoring tumor growth, development, and life span. The in vitro effects were measured through cell growth kinetics, cell proliferation, mitochondrial membrane potential disruption assay, and light and scanning electron microscopy. All drug treatments extended the mean life span of the 4T1-inoculated tumor- bearing mice; however, only tamoxifen and combination treatments statistically increased the life span when compared to untreated mice. Although the most drug inhibitory effect on cell multiplication was observed in the combination treatment, both anastrozole and tamoxifen individually inhibited cell proliferation significantly at most time periods in this mouse breast cancer cell line. The mitochondrial membrane potential disruption assay demonstrated significant increase in the percent of cells undergoing apoptosis in all treatment groups. However, the combination treatment was the most effective in inducing cell death via apoptosis. Light and scanning electron microscopy of the treated cells revealed characteristics such as rounding, clumping, and shrinkage of the