Temozolomide-induced inhibition of pituitary adenoma cells.
OBJECTIVE
Aggressive pituitary adenomas frequently require multimodality treatment including pituitary-suppressive medications, microsurgery, and radiation therapy or radiosurgery. The effectiveness of temozolomide in terms of growth suppression and decreased hormonal production is evaluated.


METHODS
Three pituitary adenoma cell lines--MMQ, GH3, and AtT20--were used. A dose escalation of temozolomide was performed for each cell line, and inhibition of cell proliferation was assessed using an MTT assay. Concentrations of temozolomide that produced statistically significant inhibition of cell proliferation for each cell type were identified. Extent of apoptosis for each selected temozolomide concentration was studied using TUNEL staining. The effect of temozolomide on prolactin secretion in MMQ and GH3 cells was also measured via ELISA.


RESULTS
Significant inhibition of cell proliferation was noted for MMQ and GH3 cells at a concentration of 250 μM temozolomide. The AtT20 cells demonstrated statistically significant cell inhibition at a concentration of only 50 μM temozolomide (p < 0.05). Apoptosis significantly increased in all cell lines in as little as 24 hours of incubation at the respective temozolomide concentrations (p < 0.05). Prolactin secretion in the prolactin secreting MMQ and GH3 cell lines was inhibited by 250 μM temozolomide.


CONCLUSIONS
Temozolomide inhibits cell proliferation and induces apoptotic cell death in aggressive pituitary adenoma cells. A reduction in hormonal secretion in prolactinoma cells was also afforded by temozolomide. Temozolomide may prove useful in the multimodality management of aggressive pituitary adenomas.
Sheehan
Jason
J
Department of Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA. jps2f@virginia.edu
Rainey
Jessica
J
Nguyen
James
J
Grimsdale
Ruthie
R
Han
Shaojie
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D020287:In Situ Nick-End Labeling; D051379:Mice; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000378:metabolism*; D051381:Rats; D000077204:Temozolomide; D014407:Tumor Cells, Cultured
D003606:Dacarbazine; D011388:Prolactin; D000077204:Temozolomide