去铁胺在放射性乳房重建中的作用：一项肿瘤安全性研究。
The Role of Deferoxamine in Irradiated Breast Reconstruction: A Study of Oncologic Safety.
机构信息
From the Department of Surgery, Section of Plastic and Reconstructive Surgery, and the Department of Pharmacology, University of Michigan.
出版信息
Plast Reconstr Surg. 2019 Jun;143(6):1666-1676. doi: 10.1097/PRS.0000000000005647.
BACKGROUND
Radiotherapy plays an essential role in the oncologic management of breast cancer. However, patients who undergo radiotherapy experience significantly more wound complications during the reconstructive process. Deferoxamine has immense potential to up-regulate angiogenesis and improve reconstructive outcomes. The purpose of this study was to determine the impact of deferoxamine on breast cancer cell proliferation in vitro, to delineate oncologic safety concerns regarding the use of deferoxamine as a regenerative therapeutic.
METHODS
The dose-dependent effect of radiation and deferoxamine on two triple-negative breast cancer cell lines (MDA-MB-231 and MDA-MB-468) was determined by means of MTS (percentage cell viability) and tumorsphere (sphere number) analysis. Radiation therapy and deferoxamine were delivered both individually and in combination, and all experiments were completed in triplicate. Intracellular iron, nuclear factor-κB localization, and apoptosis/necrosis assays were performed to delineate mechanism. Analysis of variance statistical analysis was performed using SPSS (p < 0.05).
RESULTS
For both cell lines, percentage viability and sphere number significantly decreased following exposure to 10 Gy of radiation. Surprisingly, the administration of 25 µM deferoxamine also significantly decreased each metric. The administration of deferoxamine (100 µM) in combination with radiation (10 Gy) resulted in significantly reduced percentage viability and sphere number compared with the administration of radiation alone. Deferoxamine treatment decreased intracellular iron, suppressed nuclear factor-κB activation, and induced apoptosis.
CONCLUSION
Radiation and deferoxamine significantly decrease breast cancer proliferation when delivered independently and in combination, suggesting deferoxamine may be safely used to facilitate improved reconstructive outcomes among triple-negative breast cancer survivors.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.
背景
放射治疗在乳腺癌的肿瘤治疗管理中起着至关重要的作用。然而，接受放射治疗的患者在重建过程中会经历更多的伤口并发症。去铁胺具有巨大的潜力来上调血管生成并改善重建结果。本研究的目的是确定去铁胺对体外乳腺癌细胞增殖的影响，阐明关于将去铁胺用作再生治疗的肿瘤安全性问题。
方法
通过 MTS（细胞活力百分比）和肿瘤球（球数）分析来确定辐射和去铁胺对两种三阴性乳腺癌细胞系（MDA-MB-231 和 MDA-MB-468）的剂量依赖性影响。单独和联合使用放射治疗和去铁胺进行治疗，所有实验均重复三次。进行细胞内铁、核因子-κB 定位和细胞凋亡/坏死测定以阐明作用机制。使用 SPSS 进行方差分析统计分析（p<0.05）。
结果
对于两种细胞系，暴露于 10 Gy 辐射后，细胞活力百分比和球数均显著降低。令人惊讶的是，25 µM 去铁胺的给药也显著降低了每个指标。与单独给予辐射相比，给予去铁胺（100 µM）联合辐射（10 Gy）导致细胞活力百分比和球数显著降低。去铁胺处理降低了细胞内铁，抑制了核因子-κB 激活，并诱导了细胞凋亡。
结论
单独和联合给予辐射和去铁胺可显著降低乳腺癌的增殖，这表明去铁胺可安全用于改善三阴性乳腺癌幸存者的重建结果。
临床问题/证据水平：治疗，V。
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