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二甲双胍可能保护非糖尿病乳腺癌女性免受转移。

Metformin may protect nondiabetic breast cancer women from metastasis.

作者信息

El-Haggar Sahar Mohammed, El-Shitany Nagla A, Mostafa Mohamed Farouk, El-Bassiouny Noha Ahmed

机构信息

Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.

出版信息

Clin Exp Metastasis. 2016 Apr;33(4):339-57. doi: 10.1007/s10585-016-9782-1. Epub 2016 Feb 22.

Abstract

Metformin, a widely prescribed oral hypoglycemic agent, has recently received a big interest because of its potential antitumorigenic effects in different cancer types. The present study investigated the impact of adding metformin to breast cancer adjuvant therapy in nondiabetic women on, insulin like growth factor-1 (IGF-1), IGF binding protein-3 (IGFBP-3), insulin, fasting blood glucose (FBG), the molar ratio of IGF-1 to IGFBP-3, homeostatic model assessment of insulin resistance (HOMA-IR) and metastasis. 102 women with newly diagnosed breast cancer were divided into 2 main groups, a control group and a metformin group. All women were treated with adjuvant therapy, according to the protocols of Ministry of Health and Population and National Cancer Institute, Egypt. Moreover, the women in the metformin group received 850 mg of metformin twice daily. Blood samples were collected at baseline, after chemotherapy (CT), after 6 months of hormonal therapy (6-HT) and 12 months of hormonal therapy (12-HT) for analysis of serum IGF-1, IGFBP-3, insulin, FBG and cancer antigen 15-3 (CA15-3). Metformin resulted in a significant reduction of IGF-1, IGF-1: IGFBP-3 molar ratio, insulin, FBG and HOMA-IR. On the other hand, metformin caused a significant increase of IGFBP-3. Moreover, metformin significantly decreased the numbers of metastatic cases after 6-HT. Metformin may have potential antitumor and antimetastatic effects that need further clinical investigations. This may be attributed to either the significant increase of the apoptotic inducer IGFBP-3 or/and the significant reduction of mitogenic insulin, IGF-1, free bioactive IGF-1, FBG and HOMA-IR.

摘要

二甲双胍是一种广泛使用的口服降糖药,由于其在不同癌症类型中潜在的抗肿瘤作用,最近受到了广泛关注。本研究调查了在非糖尿病女性乳腺癌辅助治疗中添加二甲双胍对胰岛素样生长因子-1(IGF-1)、IGF结合蛋白-3(IGFBP-3)、胰岛素、空腹血糖(FBG)、IGF-1与IGFBP-3的摩尔比、胰岛素抵抗稳态模型评估(HOMA-IR)和转移的影响。102例新诊断的乳腺癌女性被分为两个主要组,即对照组和二甲双胍组。所有女性均按照埃及卫生和人口部以及国家癌症研究所的方案接受辅助治疗。此外,二甲双胍组的女性每天两次服用850毫克二甲双胍。在基线、化疗后(CT)、激素治疗6个月后(6-HT)和激素治疗12个月后(12-HT)采集血样,以分析血清IGF-1、IGFBP-3、胰岛素、FBG和癌抗原15-3(CA15-3)。二甲双胍导致IGF-1、IGF-1:IGFBP-3摩尔比、胰岛素、FBG和HOMA-IR显著降低。另一方面,二甲双胍使IGFBP-3显著增加。此外,二甲双胍在6-HT后显著减少了转移病例的数量。二甲双胍可能具有潜在的抗肿瘤和抗转移作用,需要进一步的临床研究。这可能归因于凋亡诱导剂IGFBP-3的显著增加或/和促有丝分裂胰岛素、IGF-1、游离生物活性IGF-1、FBG和HOMA-IR的显著降低。

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