期刊
INTERNATIONAL JOURNAL OF HYPERTHERMIA
卷 31, 期 8, 页码 909-919出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/02656736.2015.1075072
关键词
Apoptotic death; AKT/HSP90; in vivo imaging; magnetic hyperthermia therapy; magnetic nanoparticles; tumour growth inhibition
资金
- Bhabha Atomic Research Centre, Department of Atomic Energy, Government of India
Purpose: We have evaluated the hyperthermia efficacy of oleic acid-functionalised Fe3O4 magnetic nanoparticles (MN-OA) under in vivo conditions and elucidated the underlying mechanism of tumour growth inhibition. Materials and methods: The efficacy and mechanism of tumour growth inhibition by MN-OA-mediated magnetic hyperthermia therapy (MHT) was evaluated in a murine fibrosarcoma tumour model (WEHI-164) using techniques such as TUNEL assay, Western blotting (WB), immunofluorescence (IF) staining and histopathological examination. In addition, bio-distribution of MN-OA in tumour/other target organs and its effect on normal organ function were studied by Prussian blue staining and serum biochemical analysis, respectively. Results: MN-OA-induced MHT resulted in significant inhibition of tumour growth as determined by measurement of tumour volume, as well as by in vivo imaging of tumour derived from luciferase-transfected WEHI-164 cells. Histopathology analysis showed presence of severe apoptosis and reduced tumour cells proliferation, which was further confirmed by TUNEL assay, reduced expression of Ki-67 and enhanced level of cleaved caspase-3, in tumours treated with MHT. Moreover, expression of heat stress marker, Hsp90 and its client protein, AKT/PKB was reduced by approximate to 50 and 80%, respectively, in tumours treated with MHT as studied by WB and IF staining. Serum analysis suggested insignificant toxicity of MN-OA (in terms of liver and kidney function), which was further correlated with minimal accumulation of MN-OA in target organs. Conclusions: These results suggest the involvement of apoptosis and Hsp90/AKT modulation in MN-OA-mediated MHT-induced tumour growth inhibition.
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