文章基本信息

标题：Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation
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作者：Theodore Hu ; Young Min Chung ; Michelle Guan 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：4
期号：1
DOI：10.1038/srep05810
语种：English
出版社：Springer Nature
摘要：Cancer is a leading cause of death worldwide. Because the cytotoxic effects of conventional chemotherapies often harm normal tissue cells along with cancer cells, conventional chemotherapies cause many unwanted or intolerable side effects. Thus, there is an unmet medical need to establish a paradigm of chemotherapy-induced differentiation of cancer cells with tolerable side effects. Here we show that low-dose metformin or SN-38 inhibits cell growth or survival in ovarian and breast cancer cells and suppresses their tumor growth in vivo . Low-dose metformin or SN-38 increases FOXO3 nuclear localization as well as the amount of DNA damage markers and downregulates the expression of a cancer-stemness marker CD44 and other stemness markers, including Nanog, Oct-4, and c-Myc, in these cancer cells. This treatment also inhibits spheroid body-formation in 3-dimensional culture. In contrast, silencing FOXO3 diminishes all these cellular events when ovarian/breast cancer cells are treated with the mentioned drugs. These results suggest that low-dose metformin or SN-38 may reprogram these cancer cells into non-cancerous cells in a FOXO3-dependent manner, and may allow patients to overcome these cancers with minimal side effects.