antiproliferative effects of fluoxetine on colon cancer cells and in a colonic carcinogen mouse model氟西汀对结肠癌细胞的抗增殖影响和结肠致癌物小鼠模型.pdf

Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model 1,2 2 3 3 ´ 1 Vinicius Kannen , Henning Hintzsche , Dalila L. Zanette , Wilson A. Silva Jr. , Sergio B. Garcia , Ana 4 2 Maria Waaga-Gasser , Helga Stopper * ˜ ˜ ˜ 1 Department of Pathology, Medical School of Ribeirao Preto, University of Sao Paulo, Ribeirao Preto, Brazil, 2 Department of Toxicology, University of Wuerzburg, ˜ Wuerzburg, Germany, 3 National Institute of Science and Technology in Stem Cell and Cell Therapy, CNPq/FAPESP, Department of Genetics, Medical School of Ribeirao ˜ ˜ Preto, University of Sao Paulo, Ribeirao Preto, Brazil, 4 Department of Surgery I, Molecular Oncology and Immunology, University of Wuerzburg, Wuerzburg, Germany Abstract The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) as models. Fluoxetine increas