© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 134-141, Copyright © 1998 by Oxford University Press
WD Yu, MC McElwain, RA Modzelewski, DM Russell, DC Smith, DL Trump and CS Johnson
BACKGROUND: The active metabolite of vitamin D, i.e., 1,25-
dihydroxycholecalciferol (1,25-D3), inhibits the growth of murine SCCVII/SF
squamous cell carcinoma cells, both in vitro and in vivo. However, in vivo
use of 1,25-D3 is hampered as a result of hypercalcemia (i.e., elevated
levels of calcium in the blood). Glucocorticoids, such as dexamethasone,
affect calcium absorption and modulate vitamin D receptor binding and have
been used to treat hypercalcemia. In this study, we examined the effect of
dexamethasone on tumor growth inhibition by 1,25-D3. METHODS: The effects
of 1,25-D3 and dexamethasone, alone and in combination, on the growth of
SCCVII/SF cells in in vitro culture or in vivo in female C3H/HeJ mice were
determined by clonogenic tumor cell assay and/or by actual changes in tumor
volume. Vitamin D receptor-ligand-binding activities in whole- cell
extracts from cells (in culture), tumors, and normal tissues were assayed
by single-point saturation analysis and equilibrium binding. RESULTS:
Treatment of cultured SCCVII/SF cells with 500 nM dexamethasone for 24
hours before addition of 1,25-D3 reduced their survival. The growth of
SCCVII/SF tumors was inhibited in mice treated simultaneously with
dexamethasone and 1,25-D3 (as compared with no treatment or single-agent
treatment); hypercalcemia was also reduced. Total vitamin D receptor
content in SCCVII/SF cells was increased after treatment with
dexamethasone. Treatment of tumor-bearing animals with dexamethasone (9
microg/day) for 7 days led to increased vitamin D receptor-ligand-binding
activities in whole-cell extracts from tumor or kidneys and decreased
activity in intestinal mucosa. CONCLUSIONS: Dexamethasone may enhance the
antitumor effect of 1,25-D3 by increasing vitamin D receptor-ligand-binding
activity.
ARTICLES
Enhancement of 1,25-dihydroxyvitamin D3-mediated antitumor activity with dexamethasone
Department of Otolaryngology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, PA 15213, USA.
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