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轻度微波消融联合 HSP90 和 TGF-β1 抑制剂增强骨肉瘤的治疗效果。

Mild microwave ablation combined with HSP90 and TGF‑β1 inhibitors enhances the therapeutic effect on osteosarcoma.

机构信息

The Graduate School of Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.

Guangdong Key Laboratories of Orthopedic Technology and Implant Materials, General Hospital of Southern Theater Command of PLA, Guangzhou, Guangdong 510010, P.R. China.

出版信息

Mol Med Rep. 2020 Aug;22(2):906-914. doi: 10.3892/mmr.2020.11173. Epub 2020 May 22.

Abstract

Osteosarcoma is the most common malignant bone tumour and the second leading cause of cancer‑related death in children and adolescents. Microwave ablation has an excellent therapeutic effect on bone tumours by instantaneously increasing the temperature in the tumour; however, there is a risk of damaging the surrounding healthy tissues by exposure to a high temperature when the treatment power is too large. In the present study, two anti‑tumour reagents, a heat shock protein 90 (HSP90) inhibitor (PF‑04929113) and a transforming growth factor‑β1 (TGF‑β1) inhibitor (SB‑525334) were employed to enhance the therapeutic effect of mild‑power microwave ablation. It was revealed that microwaving to 48˚C combined with HSP90 and TGF‑β1 inhibitors significantly increased the apoptotic rate of VX2 cells. The same results were observed during in vivo experiments using New Zealand rabbits to model osteosarcoma. In addition, the results indicated that the expression of cytochrome c, caspase‑3 and caspase‑9 were upregulated in response to the treatment, which indicated that the mitochondrial apoptotic signalling pathway had been activated. These findings may provide a novel strategy for the development of microwave ablation in osteosarcoma treatment, which could effectively kill tumour cells without damaging the surrounding normal tissues.

摘要

骨肉瘤是最常见的恶性骨肿瘤,也是儿童和青少年癌症相关死亡的第二大主要原因。微波消融通过瞬间提高肿瘤内的温度对骨肿瘤具有极好的治疗效果;然而,当治疗功率过大时,暴露于高温会有损伤周围健康组织的风险。在本研究中,使用了两种抗肿瘤试剂,一种是热休克蛋白 90(HSP90)抑制剂(PF-04929113)和一种转化生长因子-β1(TGF-β1)抑制剂(SB-525334),以增强低功率微波消融的治疗效果。结果表明,微波加热至 48°C 结合 HSP90 和 TGF-β1 抑制剂可显著提高 VX2 细胞的凋亡率。在使用新西兰兔建立骨肉瘤模型的体内实验中也观察到了相同的结果。此外,结果表明,细胞色素 c、半胱天冬酶-3 和半胱天冬酶-9 的表达上调,表明线粒体凋亡信号通路已被激活。这些发现可能为骨肉瘤治疗中微波消融的发展提供一种新策略,可以有效地杀死肿瘤细胞而不损伤周围正常组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d229/7339669/cac372eecc0c/MMR-22-02-0906-g00.jpg

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