title: Magnetic nanoparticle-mediated hyperthermia therapy induces tumour growth inhibition by apoptosis and Hsp90/AKT modulation.
abstract: OBJECTIVE
  We have evaluated the hyperthermia efficacy of oleic acid-functionalised Fe(3)O(4) magnetic nanoparticles (MN-OA) under in vivo conditions and elucidated the underlying mechanism of tumour growth inhibition.
  
  
  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 ∼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.
authors.affiliation: a Radiation Biology and Health Sciences Division , Bhabha Atomic Research Centre , Trombay , Mumbai , India .
authors.forename: Neena G
authors.initials: NG
authors.lastname: Shetake
authors.affiliation: a Radiation Biology and Health Sciences Division , Bhabha Atomic Research Centre , Trombay , Mumbai , India .
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: c Advanced Centre for Training, Research and Education in Cancer (ACTREC), Tata Memorial Centre , Navi Mumbai , India.
authors.forename: Snehal
authors.initials: S
authors.lastname: Gaikwad
authors.affiliation: c Advanced Centre for Training, Research and Education in Cancer (ACTREC), Tata Memorial Centre , Navi Mumbai , India.
authors.forename: Pritha
authors.initials: P
authors.lastname: Ray
authors.affiliation: a Radiation Biology and Health Sciences Division , Bhabha Atomic Research Centre , Trombay , Mumbai , India .
authors.forename: Sejal
authors.initials: S
authors.lastname: Desai
authors.affiliation: b Chemistry Division , Bhabha Atomic Research Centre , Mumbai , India , and.
authors.forename: Raghumani Singh
authors.initials: RS
authors.lastname: Ningthoujam
authors.affiliation: b Chemistry Division , Bhabha Atomic Research Centre , Mumbai , India , and.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Vatsa
authors.affiliation: a Radiation Biology and Health Sciences Division , Bhabha Atomic Research Centre , Trombay , Mumbai , India .
authors.forename: Badri N
authors.initials: BN
authors.lastname: Pandey
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006979:Hyperthermia, Induced; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D018841:HSP90 Heat-Shock Proteins; D058185:Magnetite Nanoparticles; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT/HSP90; Apoptotic death; in vivo imaging; magnetic hyperthermia therapy; magnetic nanoparticles; tumour growth inhibition