Targeted Antiosteosarcoma Methotrexate-bisphosphonate Conjugate induces apoptosis of osteosarcoma cells in vitro

X.-N. Yang, J.-C. Zeng, Y.-C. Song, H. Zhang, F.-X. Pei

Orthopedic Department, Xuzhou No. 1 Hospital, Xuzhou, China. tomzeng5@163.com

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• Oncology

OBJECTIVES: To investigate the effect of targeted antiosteosarcoma methotrexate-bisphosphonate conjugate on growth inhibition and apoptosis in human osteosarcoma MG-63 cells.

MATERIALS AND METHODS: MG-63 cells were treated with various concentrations of methotrexate-bisphosphonate conjugate and apoptosis was monitored via an MTT assay, cell morphology, TUNEL assay and flow cytometry analysis.

RESULTS: The survival rate of MG-63 cells treated for 24 to 96 hours with 2000 mg/ml or more of methotrexate-bisphosphonate conjugate decreased significantly. Cells treated with conjugate showed typical apoptotic features using inverted phase contrast microscopy and fluorescence staining, and the majority of cells demonstrated a positive result in the TUNEL assay. Karyopyknosis and crescent aggregation of chromatin were observed in conjugate-treated cells by electron microscopy. Flow cytometry of MG-63 cells treated with methotrexate-bisphosphonate conjugate showed a time and dose-dependent increase in apoptosis (p < 0.05).

CONCLUSIONS: A targeted antiosteosarcoma methotrexate-bisphosphonate conjugate induces apoptosis in human osteosarcoma MG-63 cells. This new conjugate is a valuable experimental tool for the therapy of osteosarcoma.

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