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

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.

• Authors: Lingling Chen, Ming Wang, Zefeng Lin, Mengyu Yao, Wanshun Wang, Shi Cheng, Binglin Li, Yu Zhang, Qingshui Yin
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 22 Issue 2 Pg. 906-914 (08 2020) ISSN: 1791-3004 [Electronic] Greece
• PMID: 32468060 (Publication Type: Journal Article)

Chemical References

• 6-(2-tert-butyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline
• Benzamides
• HSP90 Heat-Shock Proteins
• Imidazoles
• Indazoles
• Quinoxalines
• TGFB1 protein, human
• Transforming Growth Factor beta1
• SNX-5422
• Glycine

Topics

• Animals
• Apoptosis (drug effects, radiation effects)
• Benzamides (therapeutic use)
• Bone Neoplasms (therapy)
• Cell Line, Tumor
• Cell Survival (drug effects, radiation effects)
• Disease Models, Animal
• Glycine (therapeutic use)
• HSP90 Heat-Shock Proteins (antagonists & inhibitors, metabolism)
• Humans
• Imidazoles (therapeutic use)
• Indazoles (therapeutic use)
• Microwaves (therapeutic use)
• Osteosarcoma (therapy)
• Quinoxalines (therapeutic use)
• Rabbits
• Radiofrequency Ablation (methods)
• Transforming Growth Factor beta1 (antagonists & inhibitors, metabolism)
• Tumor Burden (drug effects, radiation effects)