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抑制肿瘤血管生成:二甲双胍对乳腺癌的预防作用

Attenuating tumour angiogenesis: a preventive role of metformin against breast cancer.

作者信息

Gao Shan, Jiang Jingcheng, Li Pan, Song Huijuan, Wang Weiwei, Li Chen, Kong Deling

机构信息

Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China.

出版信息

Biomed Res Int. 2015;2015:592523. doi: 10.1155/2015/592523. Epub 2015 Mar 25.

Abstract

Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed by in vivo assessment of metformin on tumour growth using xenograft breast cancer models. Significant inhibitory impact of metformin was observed in MCF-7, HeLa, and SKOV-3 cells, suggesting an antiproliferative property of metformin against breast, cervical, and ovarian tumour cells, respectively, with the breast tumour cells, MCF-7, being the most responsive. In vivo assessment was subsequently carried out, where mice with breast tumours were treated with metformin (20 mg/kg body weight) or sterile PBS solution for 15 consecutive days. No inhibition of breast tumour progression was detected. However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours. Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis.

摘要

二甲双胍是治疗2型糖尿病最常用的抗糖尿病药物之一。尽管有几项研究也报告了该抗糖尿病药物缺乏抗癌特性,但最近二甲双胍在肿瘤发生过程中的关键作用已被证实。鉴于二甲双胍对肿瘤进展潜在作用存在争议,研究了二甲双胍对乳腺癌、宫颈癌和卵巢癌细胞系的影响,随后使用异种移植乳腺癌模型对二甲双胍在体内对肿瘤生长的作用进行了评估。在MCF-7、HeLa和SKOV-3细胞中观察到二甲双胍有显著的抑制作用,表明二甲双胍分别对乳腺癌、宫颈癌和卵巢癌细胞具有抗增殖特性,其中乳腺癌细胞MCF-7反应最为敏感。随后进行了体内评估,给患有乳腺肿瘤的小鼠连续15天注射二甲双胍(20毫克/千克体重)或无菌PBS溶液。未检测到对乳腺肿瘤进展的抑制作用。然而,二甲双胍治疗组的肿瘤坏死显著增加,同时肿瘤内的毛细血管形成减少。因此,尽管二甲双胍对肿瘤进展缺乏短期益处,但暗示其对乳腺癌有预防作用,这部分归因于肿瘤血管生成的减弱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bae2/4389975/f9b505c0a048/BMRI2015-592523.001.jpg

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