Cytotoxic effect of methotrexate and its solvent on osteosarcoma cells in vitro.
Bone tumours may recur locally even after wide surgical excision and systemic chemotherapy. Local control of growth may be accomplished by the addition of cytostatic drugs such as methotrexate (MTX) to bone cement used to fill the defect after surgery and to stabilise the reconstructive prosthesis. We have studied the elution kinetics of MTX and its solvent N-methyl-pyrrolidone (NMP) from bone cement and their biological activities in five cell lines of osteosarcoma and in osteoblasts, and compared them with the effects of the parent compounds alone and in combination. Our findings show that MTX is released continuously over months at concentrations highly cytotoxic to osteosarcoma cells and suggest that the impregnated bone cement would be effective in the long term. Proliferating osteoblasts, however, were much less sensitive towards MTX. The dose-response relationship for NMP and experiments with MTX/NMP-mixtures show that the eluted concentrations of solvent are not toxic and do not influence the effects of MTX. We suggest that bone cement containing MTX dissolved in NMP releases the drug in a suitable and effective way and may be of value in the treatment of bone tumours.
Decker
S
S
Laboratory for Experimental Orthopaedic Research, Westfälische-Wilhelms Universität, Münster, Germany.
Winkelmann
W
W
Nies
B
B
van Valen
F
F
D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D001843:Bone Cements; D001859:Bone Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D006801:Humans; D066298:In Vitro Techniques; D008727:Methotrexate / Q000493:pharmacokinetics / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D012516:Osteosarcoma / Q000473:pathology*; D011760:Pyrrolidinones / Q000493:pharmacokinetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D000964:Antimetabolites, Antineoplastic; D001843:Bone Cements; D004343:Drug Implants; D011760:Pyrrolidinones; C038678:N-methylpyrrolidone; D008727:Methotrexate