Reprogramming ovarian and breast cancer cells into non-cancerous cells by low-dose metformin or SN-38 through FOXO3 activation

被引：44

作者：

Hu, Theodore ^{[1
]}

Chung, Young Min ^{[1
]}

Guan, Michelle ^{[1
]}

Ma, Michael ^{[1
]}

Ma, Jessica ^{[1
]}

Berek, Jonathan S. ^{[1
]}

Hu, Mickey C-T. ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Div Gynecol Oncol, Stanford, CA 94305 USA

来源：

SCIENTIFIC REPORTS | 2014年 / 4卷

基金：

美国国家卫生研究院;

关键词：

TRANSCRIPTION FACTORS; PROTEIN-KINASE; STEM-CELLS; TOPOISOMERASE-I; COLON-CANCER; STAGE-III; GROWTH; PACLITAXEL; CISPLATIN; CAMPTOTHECIN;

D O I：

10.1038/srep05810

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

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.

引用

页数：13

共 57 条

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