Targeted antiosteosarcoma methotrexate-bisphosphonate conjugate induces apoptosis of osteosarcoma cells in vitro.

Abstract

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.

• Authors: X-N Yang, J-C Zeng, Y-C Song, H Zhang, F-X Pei
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 18 Issue 15 Pg. 2116-23 ( 2014) ISSN: 2284-0729 [Electronic] Italy
• PMID: 25070815 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diphosphonates
• methotrexate bisphosphonate
• Methotrexate

Topics

• Apoptosis (drug effects)
• Bone Neoplasms (drug therapy)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Diphosphonates (pharmacology)
• Humans
• Methotrexate (analogs & derivatives, pharmacology)
• Osteosarcoma (drug therapy)
• Survival Rate