Downregulation of growth differentiation factor-15 in trichostatin A-induced apoptosis could play a role in progression of gastric cancer.
OBJECTIVE
To investigate the effect of trichostatin A (TSA) on gastric cancer cell line BGC-823, and identify the differentially expressed genes induced by TSA, which might participate in the progression of gastric cancer.


METHODS
MTT, fluorescence microscopy, and flow cytometry were used to detect the effect of TSA on growth inhibition and apoptosis of BGC-823 cells. Using gene microarray, we analyzed the changes in gene expression. Change in growth differentiation factor-15 (GDF-15) was verified by qRT-PCR and Western blotting. The expression of GDF-15 in gastric cancer and adjacent normal tissues was detected by immunohistochemistry.


RESULTS
Apoptosis of BGC-823 cells induced by TSA (75 ng/mL for 48 h) was demonstrated by flow cytometry. There were significant variations between TSA treated groups and control groups (P = 0.02). Nuclear chromatin condensation and fluorescence intensity were observed by fluorescence microscopy. GDF-15 gene expression and protein level were significantly reduced in the TSA treated group (75 ng/mL for 48 h). Immunohistochemistry demonstrated that the expression of GDF-15 in gastric adenocarcinoma was significantly higher than in the surrounding normal tissues (P < 0.05).


CONCLUSIONS
Lower GDF-15 gene expression due to TSA-induced apoptosis was found in gastric cancer cell line BGC-823. Higher GDF-15 gene expression was seen in gastric adenocarcinoma tissues.
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150080, Heilongjiang Province, China.
Yun-Long
YL
Li
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150080, Heilongjiang Province, China.
Wu
W
Cui
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150080, Heilongjiang Province, China.
Feng
F
Gao
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150080, Heilongjiang Province, China.
Zhi-Gang
ZG
Cao
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150080, Heilongjiang Province, China.
Xiao-Lin
XL
Li
Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University Harbin 150080, Heilongjiang Province, China.
Wen-Xue
WX
Zhou
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D055436:Growth Differentiation Factor 15 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D006877:Hydroxamic Acids; C012589:trichostatin A
BGC-823; Gastric cancer; apoptosis; growth differentiation factor-15; trichostatin A