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Effect of trichostatin a on SGC-7901 gastric cancer cells
Yun-Long Li1, Tong-Shu Yang2, Wei-Min Ruan1
1Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150081, Heilongjiang Province, China.
Aim:
To explore Trichostatin A (TSA) effect on SGC-7901 gastric cancer cells.
Methods:
MTT, fluorescence microscopy, and flow cytometry were used to assess TSA effect on cell growth and apoptosis in SGC-7901. Immunocytochemistry was used to evaluate the expression of acetylated histone H4 in SGC-7901 cells.Gene expression profile was determined by microarray assays. Glycoprotein hormones alpha subunit (CGA) gene and protein expressions in SGC-7901 cells were evaluated by Real-time PCR and Western blot, respectively. In addition, CGA protein levels in gastric adenocarcinoma and normal adjacent tissues were assessed by immunohistochemistry.
Results:
TSA inhibited SGC-7901 cell growth. In addition, cell proliferation was significantly decreased (P = 0.02) in TSA treatment groups (0.93 ± 0.07) compared with controls (1.15 ± 0.07). Apoptosis related morphological changes, including nuclear chromatin condensation and fluorescence strength, were observed by fluorescence microscopy. These findings corroborated the increased expression of acetylated histone H4 observed in TSA treated cells compared to controls, as determined by immunocytochemistry. Interestingly, treatment of SGC-7901 cells with TSA (75 ng/ml) resulted in CGA gene down-regulation (P = 0.0381). Accordingly, CGA protein levels were decreased in TSA treated SGC-7901 cells. Finally, immunohistochemistry analysis showed that CGA expression was significantly higher in gastric adenocarcinoma tissues than normal adjacent tissues (P = 0.001).
Conclusion:
TSA induces cell apoptosis and increases the levels of acetylated histone H4 in SGC-7901 cells. In addition, TSA treatment decreases the expression in gastric cancer cells of the CGA gene, which is upregulated in gastric adenocarcinoma tissues.
Insights
Trichostatin A (TSA) induces apoptosis and increases acetylated histone H4 in gastric cancer cells. TSA also down-regulates the glycoprotein hormones alpha subunit (CGA) gene, which is elevated in adenocarcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Gastric cancer is a significant global health concern.
- Understanding the molecular mechanisms of gastric cancer progression is crucial for developing targeted therapies.
- Trichostatin A (TSA) is a known histone deacetylase inhibitor with potential anti-cancer properties.
Purpose of the Study:
- To investigate the effects of Trichostatin A (TSA) on SGC-7901 gastric cancer cells.
- To evaluate TSA's impact on cell growth, apoptosis, and the expression of specific genes and proteins.
Main Methods:
- Cell viability was assessed using MTT assays.
- Apoptosis and cell morphology were analyzed via fluorescence microscopy and flow cytometry.
- Histone acetylation, gene expression (CGA), and protein levels (CGA) were determined using immunocytochemistry, Real-time PCR, Western blot, and microarray assays.
- CGA protein levels in clinical tissues were examined by immunohistochemistry.
Main Results:
- TSA significantly inhibited SGC-7901 cell growth and proliferation.
- TSA treatment led to increased acetylated histone H4 levels and induced apoptosis in gastric cancer cells.
- TSA down-regulated the expression of the glycoprotein hormones alpha subunit (CGA) gene and protein in SGC-7901 cells.
- CGA expression was significantly higher in gastric adenocarcinoma tissues compared to normal adjacent tissues.
Conclusions:
- TSA exhibits anti-cancer effects by inducing apoptosis and increasing histone acetylation in gastric cancer cells.
- TSA reduces the expression of CGA, a gene that is overexpressed in gastric adenocarcinoma.
- These findings suggest TSA's potential as a therapeutic agent for gastric cancer, possibly by targeting CGA.
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