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In vitro and in vivo effects of photodynamic therapy on metastatic breast cancer cells pre-treated with zoledronic acid.

Photodiagnosis and photodynamic therapy (2014-09-02)
Margarete K Akens, Lisa Wise-Milestone, Emily Won, Joerg Schwock, Albert J M Yee, Brian C Wilson, Cari M Whyne
ABSTRACT

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. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Verteporfin, ≥94% (HPLC)
Sigma-Aldrich
Calcein-AM, BioReagent, suitable for fluorescence, ≥95.0% (HPLC)
Sigma-Aldrich
Calcein AM solution, 4 mM in DMSO, ≥90% (HPLC), solution
Sigma-Aldrich
Calcein-AM, Small Package (20 X 50 μg ), ≥95.0% (HPLC)