title: In vitro and in vivo effects of photodynamic therapy on metastatic breast cancer cells pre-treated with zoledronic acid.
abstract: BACKGROUND
  Photodynamic therapy (PDT), a non-ionizing, minimally invasive drug-light treatment, has recently been shown to successfully ablate tumor within rat vertebrae with concurrent improvements in bone strength and architecture. The bisphosphonate zoledronic acid (zol), a current drug for patients with skeletal metastases, primarily works by inhibiting osteoclast activity, but direct anti-tumor effects have also been reported. However, it is unknown if or how pre-treatment with zol may alter the tumorcidal effect of PDT. The aim of this study was to evaluate the effect of PDT, both in vitro and in vivo, on zol-pretreated cancer cells.
  
  
  METHODS
  Human metastatic breast cancer cells (MT-1) were cultured in vitro and treated with zol (10μM) for 24h, followed by PDT treatment. Cell viability was assessed by fluorescence microscopy and flow cytometry. In vivo, MT-1 cells were injected (intracardiac) into athymic rats. On day 7, zol (60μg/kg) was administered subcutaneously. On day 14, PDT was applied (1mg/kg verteporfin; 75J; 690nm) to lumbar vertebrae. Histomorphometric assessment of tumor burden was evaluated on day 21.
  
  
  RESULTS
  The cell viability measured in vitro after PDT treatment decreased in cells pre-incubated with zol up to 20% compared to treatment with PDT alone. Zol alone had no influence on the MT-1 cell viability. In vivo, all treatments, either alone or combined, had a tumorcidal effect.
  
  
  CONCLUSIONS
  Pre-treatment with zol in vivo did not yield a synergistic effect on tumor ablation in contrast to the in vitro results, but neither did it abrogate the positive tumorcidal effect of PDT, so that those therapies may be applied in combination.
authors.affiliation: Orthopaedic Biomechanics Laboratory, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. Electronic address: margarete.akens@rmp.uhn.ca.
authors.forename: Margarete K
authors.initials: MK
authors.lastname: Akens
authors.affiliation: Orthopaedic Biomechanics Laboratory, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. Electronic address: lwisemil@gmail.com.
authors.forename: Lisa
authors.initials: L
authors.lastname: Wise-Milestone
authors.affiliation: Orthopaedic Biomechanics Laboratory, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. Electronic address: emily.won85@gmail.com.
authors.forename: Emily
authors.initials: E
authors.lastname: Won
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, Canada M5G 2M9. Electronic address: joerg.schwock@gmail.com.
authors.forename: Joerg
authors.initials: J
authors.lastname: Schwock
authors.affiliation: Orthopaedic Biomechanics Laboratory, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. Electronic address: albert.yee@sunnybrook.ca.
authors.forename: Albert J M
authors.initials: AJ
authors.lastname: Yee
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON, Canada M5G 2M9. Electronic address: wilson@uhnres.utoronto.ca.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Wilson
authors.affiliation: Orthopaedic Biomechanics Laboratory, Sunnybrook Research Institute, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. Electronic address: cari.whyne@sunnybrook.ca.
authors.forename: Cari M
authors.initials: CM
authors.lastname: Whyne
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D066298:In Vitro Techniques; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage; D051381:Rats; D011923:Rats, Nude; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D017319:Photosensitizing Agents; D000077211:Zoledronic Acid
keywords: Bone metastasis; Breast cancer; Photodynamic therapy; Spine; Zoledronic acid