在激素依赖性乳腺癌细胞模型中,高葡萄糖降低芳香化酶抑制剂的抗肿瘤活性

IF 0.4 4区 医学 Q4 PHARMACOLOGY & PHARMACY
Kamila Boszkiewicz, Agnieszka Piwowar
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引用次数: 0

摘要

三分之一的乳腺癌患者还患有糖尿病,这与死亡率高出40%的风险有关。接受抗癌治疗的患者在日常生活中也会接触到异种雌激素,这可能会影响所使用治疗的有效性。我们的研究目的是分析金属雌激素(Al, Cr[III])在细胞模型中普遍存在的高糖条件下对芳香化酶抑制剂(AIs)有效性的影响。对2个人乳腺癌细胞系MCF-7和MCF-7/ DOX-a进行细胞活力测定、流式细胞仪检测细胞凋亡、ELISA检测BAX、Bcl-2和VEGF-A蛋白活性。结果采用单因素方差分析,事后采用Tukey多重比较检验。无论是否与金属雌激素联合使用,高糖条件都会降低AIs在两种细胞系中的有效性(降低细胞毒性、抑制细胞凋亡、增加Bcl-2/BAX比率和血管生成)。高血糖可能比单独使用金属雌激素更大程度地影响AIs的有效性——在高葡萄糖浓度存在时,药物活性显著降低,无论是否与金属雌激素联合使用,这表明高血糖在降低其活性方面起着关键作用。因此,控制高血糖和个体化治疗方案对癌症合并糖尿病患者可能具有重要的治疗意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
High glucose reduces anti-tumor activity of aromatase inhibitors in a hormone-dependent breast cancer cell model
One third of breast cancer patients also suffer from diabetes, which is associated with a 40% higher risk of mortality. Patients undergoing anti-cancer treatment are also exposed to xenoestrogens present in everyday life, which may affect the effectiveness of the therapies used. The purpose of our study was to analyzed the effect of metalloestrogens (Al, Cr[III]) on the effectiveness of aromatase inhibitors (AIs) under high glucose conditions prevailing in the cellular model. On two human breast cancer cell lines—MCF-7 and MCF-7/DOX—a cell viability assay, a flow cytometer analysis of apoptosis, and protein activity of BAX, Bcl-2, and VEGF-A by ELISA were carried out. Results were analyzed using one-way ANOVA, followed post hoc by Tukey’s multiple comparisons tests. High glucose conditions reduced the effectiveness of AIs in both cell lines (decreased cytotoxicity, inhibition of apoptosis, increase in Bcl-2/BAX ratio and angiogenesis), regardless of the combination with metalloestrogens. Hyperglycemia may affect the effectiveness of AIs to a greater extent than metalloestrogens alone - the activity of drugs in the presence of high glucose concentrations was significantly lower, regardless of the combination with metalloestrogens, which indicates the key role of hyperglycemia in attenuating their activity. Therefore controlling hyperglycemia and individualized treatment regimens in cancer patients with diabetes may have important therapeutic implications.
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来源期刊
CiteScore
0.80
自引率
0.00%
发文量
74
审稿时长
6-12 weeks
期刊介绍: The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General. A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.
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