Thermotherapy using magnetic cationic liposomes powerfully suppresses prostate cancer bone metastasis in a novel rat model

Prostate. 2013 Jun;73(9):913-22. doi: 10.1002/pros.22637. Epub 2013 Jan 17.

Abstract

Background: Bone metastasis is a serious problem for individuals with prostate cancer, and the effects of the anticancer drug docetaxel (DTX) are insufficient. We therefore examined the therapeutic potential of magnetic cationic liposomes (MCL) in a novel rat model that allows the evaluation of tumor immunity. The effects of MCL thermotherapy were compared with those of DTX as a conventional therapy for the treatment of bone metastatic prostate cancer.

Methods: Prostate tumor tissues were transplanted into the femurs of model rats divided into four groups: control, MCL, DTX, and MCL + DTX. Tumors were injected with MCL, and alternating magnetic field (AMF) irradiation was performed three times a week. Tumor proliferation and bone destruction were evaluated by proliferating cell nuclear antigen positivity, computed tomography, and CD68-positive cell number, while tumor immunity was evaluated by heat shock protein (HSP) 70 expression and CD8-positive lymphocyte number.

Results: We successfully established a novel femur metastasis model of prostate cancer, and demonstrated that tumor proliferation and bone destruction in the MCL and MCL + DTX groups were significantly suppressed compared with control and DTX groups. MCL thermotherapy concurrently induced necrosis and apoptosis. The expression of HSP70 in the MCL and MCL + DTX groups was also significantly increased, and tumor immunity was enhanced through the induction of CD8-positive lymphocytes.

Conclusion: MCL thermotherapy was clearly more effective than DTX in treating bone metastatic prostate cancer. A combination of MCL thermotherapy and DTX therefore deserves consideration as a novel treatment for this disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Neoplasms / secondary*
  • Bone Neoplasms / therapy*
  • Cations / administration & dosage
  • Colloids / administration & dosage*
  • Disease Models, Animal
  • Docetaxel
  • Ferrosoferric Oxide / administration & dosage*
  • Hyperthermia, Induced / methods*
  • Liposomes / administration & dosage
  • Magnetics
  • Male
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Random Allocation
  • Rats
  • Rats, Inbred F344
  • Taxoids / pharmacology

Substances

  • Cations
  • Colloids
  • Liposomes
  • Taxoids
  • Docetaxel
  • Ferrosoferric Oxide