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Effect of dexamethasone on cell proliferation of neuroepithelial tumor cell lines
A Kawamura1, N Tamaki, T Kokunai
1Department of Neurosurgery, Kobe University School of Medicine.
Abstract:
The effect of glucocorticoid on cell proliferation, the expression of glucocorticoid receptor, and the relationship between inhibition of cell growth and apoptosis were investigated in four established neuroepithelial tumor cell lines (KNS42, T98G, A172, and U251MG). Glucocorticoid receptor expression was located in the cytoplasm of untreated cells, but translocated into nuclei after treatment with dexamethasone in KNS42, T98G, and A172 cells. U251MG did not express glucocorticoid receptors. Dexamethasone significantly inhibited the growth of KNS42 and T98G cell lines, at high concentrations in contrast to growth stimulation at low concentration. Dexamethasone inhibited proliferation of A172 cell line at all concentrations from 10(-4) M to 10(-7) M. These were prevented by RU38486, a specific glucocorticoid antagonist. Apoptosis did not occur in any cell lines after dexamethasone treatment. There was no response to glucocorticoid by U251MG cells. Dexamethasone treatment of neuroepithelial tumor cells expressing glucocorticoid receptors causes translocation into the nucleus to modulate cell proliferation upon binding of different concentrations of dexamethasone in vitro. Dexamethasone inhibits proliferation of some neuroepithelial cell lines, not by glucocorticoid-induced apoptosis. The bimodal potential of glucocorticoid to stimulate or suppress proliferation of neuroepithelial tumor cells expressing glucocorticoid receptor must be considered in clinical trials.
Insights
Glucocorticoids affect neuroepithelial tumor cell growth, with dexamethasone inhibiting proliferation in some cell lines by nuclear receptor translocation, not apoptosis. This dual effect requires consideration in clinical trials.
Area of Science:
- Neuroscience
- Molecular Biology
- Oncology
Background:
- Glucocorticoids are used in cancer therapy.
- Neuroepithelial tumors express glucocorticoid receptors (GR).
- The precise effects of glucocorticoids on these tumors are not fully understood.
Purpose of the Study:
- To investigate the effect of glucocorticoids on neuroepithelial tumor cell proliferation.
- To examine glucocorticoid receptor expression and localization.
- To determine the relationship between glucocorticoid treatment, cell growth inhibition, and apoptosis.
Main Methods:
- Utilized four neuroepithelial tumor cell lines (KNS42, T98G, A172, U251MG).
- Assessed glucocorticoid receptor expression and nuclear translocation upon dexamethasone treatment.
- Measured cell proliferation and apoptosis following dexamethasone exposure at various concentrations.
- Used RU38486, a specific glucocorticoid antagonist, to block effects.
Main Results:
- Glucocorticoid receptor expression and nuclear translocation were observed in KNS42, T98G, and A172 cells, but not U251MG.
- Dexamethasone inhibited proliferation of KNS42 and T98G cells at high concentrations, but stimulated it at low concentrations.
- Dexamethasone inhibited A172 cell proliferation across all tested concentrations.
- No apoptosis was induced by dexamethasone in any cell line; effects were blocked by RU38486.
Conclusions:
- Glucocorticoid treatment leads to nuclear translocation of GR in responsive neuroepithelial tumor cells, modulating proliferation.
- Dexamethasone exhibits a bimodal effect, inhibiting or stimulating proliferation depending on concentration.
- Glucocorticoid-induced inhibition of neuroepithelial tumor cell proliferation occurs independently of apoptosis.
- The concentration-dependent, bimodal effects of glucocorticoids on tumor cell proliferation necessitate careful consideration in clinical applications.