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Anti-Tumor Effects Of Low Dose Zoledronate On Lung Cancer-Induced Spine Metastasis

Elie Akoury, Ana Sofia Ramirez Garcia Luna, Pouyan Ahangar, Xiaoya Gao, Pylyp Zolotarov, Michael H. Weber, Derek H. Rosenzweig

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Zoledronate (Zol) is an anti-resorptive/tumoral agent used for the treatment of many cancers including spinal bone metastasis. High systemic administration of a single dose is now the standard clinical care, yet it has been associated with several side effects. Here, we aimed to evaluate the effects of lower doses Zol on lung cancer and lung cancer-induced bone metastasis cells over a longer time period. Human lung cancer (HCC827) and three bone metastases secondary to lung cancer (BML1, BML3 and BML4) cells were treated with Zol at 1, 3 and 10 µM for 7 days and then assessed for cell proliferation, migration, invasion and apoptosis. Low Zol treatment significantly decreased cell proliferation (1, 3 and 10 µM), migration (3 and 10 µM) and invasion (10 µM) while increasing apoptosis (10 µM) in lung cancer and metastatic cells. Our data exploits the potential of using low doses Zol for longer treatment periods and reinforces this approach as a new therapeutic regimen to impede the development of metastatic bone cancer while limiting severe side effects following high doses of systemic drug treatment.