Research Laboratory for Biochemical Pathology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark.
Department of Surgery, Aarhus University Hospital, Aarhus, Denmark.
Breast Cancer Res Treat. 2020 May;181(1):107-113. doi: 10.1007/s10549-020-05621-6. Epub 2020 Apr 2.
Epidemiological studies and randomized clinical trials suggest that the antidiabetic drug, metformin, may have anti-neoplastic effects. The mechanism that mediates these beneficial effects has been suggested to involve direct action on cancer cells, but this will require distribution of metformin in tumor tissue. The present study was designed to investigate metformin distribution in vivo in breast and liver tissue in breast cancer patients.
Seven patients recently diagnosed with ductal carcinoma were recruited. Using PET/CT, tissue distribution of metformin was determined in vivo for 90 min after injection of a carbon-11-labeled metformin tracer. After surgery, tumor tissue was investigated for gene expression levels of metformin transporter proteins.
Tumor tissue displayed a distinct uptake of metformin compared to normal breast tissue AUC (75.4 ± 5.5 vs 42.3 ± 6.3) g/ml*min (p = 0.01). Maximal concentration in tumor was at 1 min where it reached approximately 30% of the activity in the liver. The metformin transporter protein with the highest gene expression in tumor tissue was multidrug and toxin extrusion 1 (MATE 1) followed by plasma membrane monoamine transporter (PMAT).
This study confirms that metformin is transported into tumor tissue in women with breast cancer. This finding support that metformin may have direct anti-neoplastic effects on tumor cells in breast cancer patients. However, distribution of metformin in tumor tissue is markedly lower than in liver, an established metformin target tissue.
流行病学研究和随机临床试验表明，抗糖尿病药物二甲双胍可能具有抗肿瘤作用。介导这些有益效果的机制被认为涉及对癌细胞的直接作用，但这将需要二甲双胍在肿瘤组织中的分布。本研究旨在研究乳腺癌患者体内二甲双胍在乳腺和肝脏组织中的分布。
招募了 7 名最近被诊断为导管癌的患者。使用 PET/CT，在注射碳-11 标记的二甲双胍示踪剂后 90 分钟内，在体内测定二甲双胍的组织分布。手术后，研究肿瘤组织中二甲双胍转运蛋白的基因表达水平。
与正常乳腺组织 AUC（75.4±5.5 比 42.3±6.3）g/ml*min 相比，肿瘤组织显示出明显的二甲双胍摄取（p=0.01）。肿瘤中的最大浓度出现在 1 分钟时，达到肝脏中活性的约 30%。在肿瘤组织中基因表达最高的二甲双胍转运蛋白是多药和毒素外排 1（MATE 1），其次是质膜单胺转运蛋白（PMAT）。
本研究证实，二甲双胍可被运送到乳腺癌女性的肿瘤组织中。这一发现支持二甲双胍可能对乳腺癌患者的肿瘤细胞具有直接的抗肿瘤作用。然而，二甲双胍在肿瘤组织中的分布明显低于肝脏，肝脏是已建立的二甲双胍靶组织。
