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- Title
Enhancement of 1,25-dihydroxyvitamin D3-mediated antitumor activity with dexamethasone.
- Authors
Yu, Wei-Dong; McElwain, Mariann C.; Modzelewski, Ruth A.; Russell, Derick M.; Smith, David C.; Trump, Donald L.; Johnson, Candace S.; Yu, W D; McElwain, M C; Modzelewski, R A; Russell, D M; Smith, D C; Trump, D L; Johnson, C S
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>Dexamethasone may enhance the antitumor effect of 1,25-D3 by increasing vitamin D receptor-ligand-binding activity.
- Subjects
LEUKEMIA in animals; ANIMAL experimentation; ANTINEOPLASTIC agents; CELL receptors; COMPARATIVE studies; GLUCOCORTICOIDS; HYPERCALCEMIA; RESEARCH methodology; MEDICAL cooperation; MICE; RESEARCH; SQUAMOUS cell carcinoma; EVALUATION research; DEXAMETHASONE; CALCITRIOL; DISEASE complications; PHARMACODYNAMICS
- Publication
JNCI: Journal of the National Cancer Institute, 1998, Vol 90, Issue 2, p134
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/90.2.134