Zoledr0nic Acid May Enhance the Doxorubicin Cytotoxicity Effect in Osteosarcoma Cell Line

Abstract

Background and Objectives: osteosarcoma is primary malignancy of the skeleton, commonly developing in children and adolescents.
Zoledronic acid is heterocyclic nitrogen containing bisphosphonate,have potent antiresorptive effective in bone disease such osteoporosis, Paget disease and in malignant tumor metastasis to bone. Its antitumor properties arise from the suppression of the mevalonate pathway of tumor cells. Method and Material: osteosarcoma cell line "MG". These cells were exposed to serial concentrations of zoledronic acid (500,250,125,62,31,15µg/ml) alone or in combination with doxorubicin (5µg/ml). After 24h incubation, cytotoxicity was assessed using an MTT assay, ElIZA method, are used to evaluated anti-inflamatory effect of zoledronic acid on via measurement of IL-6,and TNF-α level. Result: zoledronic acid has demonstrated a significant decrease in cell number at all serial concentration (500,250,125,62,31,15µg/m), While zoledronic acid -doxorubicin combination was applied to the cells, highly significant cytotoxic synergism was shown at all concentrations comparison control group. After evaluated by MTT assay. ELIZA method was showed zoledronic acid at high concentration decrease IL-6, TNF-α levels. Conclusion: zoledronic acid has an antiproliferation effect on MG osteosarcoma cell line at serial concentration, while zol –doxorubicin was showed significant cytotoxic synergism above 62µg/ml concentrations, and has showed zoledronic acid at high concentration have antiinflamatory properties decreasing forIL-6, TNF-α.