Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.
Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.
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DOI：
10.1158/0008-5472.can-10-3471
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发表时间：
2011-05-01
期刊：
影响因子：
11.2
通讯作者：
Struhl K
中科院分区：
文献类型：
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作者：
Iliopoulos D;Hirsch HA;Struhl K
二甲双胍是治疗糖尿病的一线药物，它选择性地杀死遗传上不同类型的乳腺癌细胞系中耐化疗的癌症干细胞亚群。在小鼠异种移植物中，在肿瘤附近注射二甲双胍和化疗药物多柔比星在阻断肿瘤生长和预防复发方面比单独使用任何一种药物都更有效。在这里，我们表明二甲双胍与紫杉醇、卡铂和多柔比星一起口服同样有效，表明二甲双胍与各种标准化疗药物一起起作用。此外，当二甲双胍与剂量减少4倍的多柔比星联合使用时，二甲双胍对肿瘤消退和预防复发的作用相当，而单药治疗无效。最后，二甲双胍和多柔比星的组合防止用前列腺癌和肺癌细胞系产生的异种移植物的复发。这些观察结果为癌症复发的癌症干细胞假说提供了进一步的证据，也为在各种临床环境中使用二甲双胍作为联合治疗的一部分以及减少癌症患者化疗剂量提供了实验依据。
Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy-resistant, sub-population of cancer stem cells in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when metformin combined with a 4-fold reduced dose of doxorubicin that is not effective as a monotherapy. Lastly, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the cancer stem cell hypothesis for cancer relapse, as well as an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings and for reducing the chemotherapy dose in cancer patients.