Abstract

15526 Background: Paricalcitol is a calcitriol analog used in the treatment of secondary hyperparathyroidism. It produces less hypercalcemia compared to calcitriol and has low clinical toxicity. We have shown previously that paricalcitol is antiproliferative in head and neck squamous cell carcinomas (HNSCC) in vitro. However, its interaction in combination with docetaxel and radiation has not been elucidated. The purpose of this study is to evaluate the combined effects of paricalcitol, docetaxel, and radiation in vitro in SCC-15 cells, a human tongue squamous cell carcinoma cell line. Methods: The cytotoxic effects were assessed using MTT assays. SCC 15 cells were plated, allowed to attach for 24 hours, and then treated with paricalcitol at 0, 12.5, 25, or 50 nM. After 24 hours, docetaxel at 0, 0.05, 0.15, or 0.3 nM was applied, followed in 24 hours by single treatment with radiation at 0, 2, 4, or 6 Gy. MTT assays were performed after incubation for 5 days. CalcuSyn analysis was used to determine if the interaction between paricalcitol, docetaxel, and radiation is synergistic, additive, or antagonistic. Results: Paricalcitol alone at 12.5, 24, and 50 nM produced growth inhibition of 30, 38, and 40%, respectively. Docetaxel alone at 0.05, 0.15, and 0.3 nM resulted in 33, 61, and 72% growth inhibition, respectively. Radiation at 2, 4, and 6 Gy produced 44, 57, and 62% inhibition, respectively. Sequential paricalcitol and docetaxel at the concentrations tested followed by 2 Gy radiation produced additive to synergistic cytotoxicity. Antagonism was seen with 4 Gy and all combinations of paricalcitol and docetaxel. Antagonism was also seen with 6 Gy and 0.15 or 0.3 nM of docetaxel. Conclusions: Sequential application of paricalcitol, docetaxel, and then radiation at moderate doses produced additive to synergistic cytotoxicity in SCC-15 cells. The results of this study provide support for further investigations of combined paricalcitol, docetaxel and radiation therapy in the treatment of head and neck cancers. [Table: see text]

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