Stapf Marcus, Pömpner Nadine, Kettering Melanie, Hilger Ingrid
Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany.
Int J Nanomedicine. 2015 Mar 10;10:1931-9. doi: 10.2147/IJN.S77372. eCollection 2015.
Magnetically induced heating of magnetic nanoparticles (MNP) in an alternating magnetic field (AMF) is a promising minimal invasive tool for localized tumor treatment that eradicates tumor cells by applying thermal stress. While temperatures between 42°C and 45°C induce apoptosis and sensitize the cells for chemo- and radiation therapies when applied for at least 30 minutes, temperatures above 50°C, so-called thermoablative temperatures, rapidly induce irreversible cell damage resulting in necrosis. Since only little is known concerning the protein expression of anti-apoptotic B-cell lymphoma 2 (BCL2), fibroblast growth factor receptor 1 (FGF-R1), and heat shock protein (HSP70) after short-time magnetic thermoablative tumor treatment, these relevant tumor proteins were investigated by immunohistochemistry (IHC) in a human BT474 breast cancer mouse xenograft model. In the investigated sample groups, the application of thermoablative temperatures (<2 minutes) led to a downregulation of BCL2 and FGF-R1 on the protein level while the level of HSP70 remained unchanged. Coincidently, the tumor tissue was damaged by heat, resulting in large apoptotic and necrotic areas in regions with high MNP concentration. Taken together, thermoablative heating induced via magnetic methods can reduce the expression of tumor-related proteins and locally inactivate tumor tissue, leading to a prospectively reduced tumorigenicity of cancerous tissues. The presented data allow a deeper insight into the molecular mechanisms in relation to magnetic thermoablative tumor treatments with the aim of further improvements.
在交变磁场（AMF）中对磁性纳米颗粒（MNP）进行磁诱导加热是一种很有前景的局部肿瘤治疗微创工具，它通过施加热应力来根除肿瘤细胞。当在42°C至45°C之间的温度持续施加至少30分钟时，会诱导细胞凋亡并使细胞对化学疗法和放射疗法敏感，而高于50°C的温度，即所谓的热消融温度，会迅速诱导不可逆的细胞损伤，导致坏死。由于关于短时间磁热消融肿瘤治疗后抗凋亡B细胞淋巴瘤2（BCL2）、成纤维细胞生长因子受体1（FGF-R1）和热休克蛋白（HSP70）的蛋白质表达了解甚少，因此在人BT474乳腺癌小鼠异种移植模型中通过免疫组织化学（IHC）研究了这些相关肿瘤蛋白。在研究的样本组中，热消融温度（<2分钟）的应用导致BCL2和FGF-R1在蛋白质水平上的下调，而HSP70的水平保持不变。巧合的是，肿瘤组织因热而受损，在高MNP浓度区域导致大量凋亡和坏死区域。综上所述，通过磁方法诱导的热消融加热可以降低肿瘤相关蛋白的表达并局部灭活肿瘤组织，从而有望降低癌组织的致瘤性。所呈现的数据有助于更深入地了解与磁热消融肿瘤治疗相关的分子机制，以期进一步改进。
