In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells.
BACKGROUND
Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells.


METHODS
Human MCF-7 breast cancer cells were treated with up to 100 microM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation.


RESULTS
Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 microM and 20 microM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis.


CONCLUSIONS
These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma.
Ural
A Ugur
AU
Department of Hematology, Gulhane Military Medical Faculty, Ankara, Turkey. aural@gata.edu.tr
Avcu
Ferit
F
Candir
Muhammed
M
Guden
Metin
M
Ozcan
M Ali
MA
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D045744:Cell Line, Tumor; D002468:Cell Physiological Phenomena / Q000187:drug effects* / Q000528:radiation effects*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D011878:Radiotherapy; D000077211:Zoledronic Acid
D000970:Antineoplastic Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid