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二甲双胍不会抑制 2 型糖尿病合并症患者乳腺癌组织中的芳香化酶表达。

[Metformin does not suppress the aromatase expression in breast cancer tissue of patients with concurrent type 2 diabetes].

作者信息

Bershteĭn L M, Turkevich E A, Boiarkina M P

出版信息

Vopr Onkol. 2012;58(2):194-8.

Abstract

Although there is data suggesting the in vitro inhibition of aromatase in cell lines by antidiabetic biguanide metformin (MF), there is no data on the intratumoral breast cancer (BC) aromatase expression in patients already receiving therapy for type II diabetes. Paraffinized tumor samples obtained from 57 BC pts aged 48-77 yrs, >80% of pts had stage T1-2N0-3M0 BC. Thirteen of the pts didn't have diabetes, 44 pts were previously diagnosed type II diabetes and reseaved the following therapy for at least 1 year: diet only (n=14), sulphonylurea (SU, n=14), metformin (MF, n=9) or MF with SU (n=7). Tumor samples were deparaffinized in xylene and treated with the monoclonal aromatase antibody 677. The rate and intensity of tissue staining was then analyzed by semi-quantitative method using conventional scores. Negative controls were processed with 0.01 M PBS instead of the specific antibody. For positive control paraffin-embedded human placenta samples were used. By conventional scores method the following values were obtained: 1.31 (pts without diabetes), 1.47 (all diabetic patients), 2.22 (MF), 1.50 (SU), 1.29 (MF+SU), 1.81 (MF and MF+SU), 1.07 (diet). Allred scores for progesterone receptor (PR) were the highest in the samples from pts treated with MF or MF+SU and the lowest in the samples obtained from SU-treated pts. Thus, in contrast to previous findings suggesting the suppressive effect of MF on aromatase in vitro, no such trend was discovered for aromatase expression in tumor samples from diabetic patients treated with MF. Although the investigated patients population is still small, this data combined with clinical data (higher PR levels) may suggest the better responses to hormonal therapy in MF-treated diabetic patients.

摘要

尽管有数据表明抗糖尿病双胍类药物二甲双胍(MF)在体外可抑制细胞系中的芳香化酶,但对于已接受II型糖尿病治疗的患者,尚无关于其肿瘤内乳腺癌(BC)芳香化酶表达的数据。从57例年龄在48 - 77岁的BC患者中获取石蜡包埋的肿瘤样本,超过80%的患者为T1 - 2N0 - 3M0期BC。其中13例患者无糖尿病,44例患者先前被诊断为II型糖尿病并接受了至少1年的以下治疗:仅饮食控制(n = 14)、磺脲类药物(SU,n = 14)、二甲双胍(MF,n = 9)或MF联合SU(n = 7)。肿瘤样本在二甲苯中脱蜡,并用单克隆芳香化酶抗体677处理。然后采用传统评分的半定量方法分析组织染色的速率和强度。阴性对照用0.01 M PBS代替特异性抗体进行处理。阳性对照使用石蜡包埋的人胎盘样本。通过传统评分方法获得以下值:1.31(无糖尿病患者)、1.47(所有糖尿病患者)、2.22(MF)、1.50(SU)、1.29(MF + SU)、1.81(MF和MF + SU)、1.07(饮食控制)。孕酮受体(PR)的Allred评分在接受MF或MF + SU治疗的患者样本中最高,而在接受SU治疗的患者样本中最低。因此,与之前表明MF在体外对芳香化酶有抑制作用的研究结果相反,在接受MF治疗的糖尿病患者的肿瘤样本中未发现芳香化酶表达有此类趋势。尽管所研究的患者群体仍然较小,但这些数据与临床数据(较高的PR水平)相结合可能表明接受MF治疗的糖尿病患者对激素治疗的反应更好。

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