Dexamethasone suppresses apoptosis in a human gastric cancer cell line through modulation of bcl-x gene expression
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T C Chang1, M W Hung, S Y Jiang
1Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, ROC.
Abstract:
Treatment of human gastric cancer TMK-1 cells with transcription and translation inhibitors rapidly triggered cell apoptosis. Along with cell apoptosis, the Bcl-xS level was markedly upregulated suggesting a crucial role of this protein in promoting the apoptotic process. In the presence of dexamethasone, however, cell apoptosis was greatly attenuated as demonstrated by DNA histogram shift and DNA fragmentation. Studies using the glucocorticoid receptor antagonist RU486 indicated that attenuation of apoptosis was mediated through glucocorticoid receptors. Dexamethasone not only suppressed the apoptosis-associated upregulation of Bcl-xS but also enhanced the basal level of Bcl-xL in the cells. In addition, bcl-x mRNA stability was significantly extended in the presence of dexamethasone. These results indicate that dexamethasone exerted a protective effect and delayed apoptosis of TMK-1 cells by modulating bcl-x gene expression.
Insights
Dexamethasone treatment protects human gastric cancer cells from apoptosis by regulating Bcl-x gene expression. This involves modulating Bcl-xS and Bcl-xL protein levels and enhancing mRNA stability via glucocorticoid receptors.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Gastric cancer is a significant health concern.
- Apoptosis is a critical process in cancer development and treatment.
- Bcl-x proteins play a role in regulating apoptosis.
Purpose of the Study:
- To investigate the effect of dexamethasone on apoptosis in human gastric cancer TMK-1 cells.
- To elucidate the role of Bcl-xS and Bcl-xL in dexamethasone-mediated apoptosis.
- To determine the involvement of glucocorticoid receptors in this process.
Main Methods:
- Treatment of TMK-1 cells with transcription/translation inhibitors.
- Assessment of cell apoptosis using DNA histogram shift and fragmentation.
- Analysis of Bcl-xS and Bcl-xL protein levels.
- Use of glucocorticoid receptor antagonist RU486.
- Measurement of bcl-x mRNA stability.
Main Results:
- Transcription and translation inhibitors rapidly induced apoptosis in TMK-1 cells.
- Bcl-xS was upregulated during apoptosis.
- Dexamethasone significantly attenuated apoptosis, suppressed Bcl-xS upregulation, and enhanced Bcl-xL levels.
- Apoptosis attenuation was mediated by glucocorticoid receptors.
- Dexamethasone extended bcl-x mRNA stability.
Conclusions:
- Dexamethasone protects gastric cancer cells from apoptosis.
- This protective effect is mediated through glucocorticoid receptors.
- Dexamethasone modulates bcl-x gene expression, including Bcl-xS and Bcl-xL, and mRNA stability to delay apoptosis.