癌症干细胞
癌症
二甲双胍
干细胞
医学
阿霉素
乳腺癌
癌细胞
癌症研究
化疗
肿瘤科
内科学
药理学
生物
胰岛素
遗传学
作者
Heather A. Hirsch,Dimitrios Iliopoulos,Philip N. Tsichlis,Kevin Struhl
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2009-10-01
卷期号:69 (19): 7507-7511
被引量:978
标识
DOI:10.1158/0008-5472.can-09-2994
摘要
Abstract The cancer stem cell hypothesis suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Thus, drugs that selectively target cancer stem cells offer great promise for cancer treatment, particularly in combination with chemotherapy. Here, we show that low doses of metformin, a standard drug for diabetes, inhibits cellular transformation and selectively kills cancer stem cells in four genetically different types of breast cancer. The combination of metformin and a well-defined chemotherapeutic agent, doxorubicin, kills both cancer stem cells and non–stem cancer cells in culture. Furthermore, this combinatorial therapy reduces tumor mass and prevents relapse much more effectively than either drug alone in a xenograft mouse model. Mice seem to remain tumor-free for at least 2 months after combinatorial therapy with metformin and doxorubicin is ended. These results provide further evidence supporting the cancer stem cell hypothesis, and they provide a rationale and experimental basis for using the combination of metformin and chemotherapeutic drugs to improve treatment of patients with breast (and possibly other) cancers. [Cancer Res 2009;69(19):7507–11]
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