[Role of histone deacetylase in inhibiting invasion of human gastric carcinoma cell line SGC-7901 by PPARgamma-mediated pathway].
OBJECTIVE
Histone deacetylase (HDAC) can attenuate the function of peroxisome proliferator-activated receptor gamma (PPARgamma) to drive adipocyte differentiation. PPARgamma activation is confirmed to inhibit the development and metastasis of a variety of malignant cells. This study was to investigate the role of HDAC in inhibiting the invasion of human gastric carcinoma SGC-7901 cells through PPARgamma-mediated pathway, and explore potential mechanism.


METHODS
SGC-7901 cells were treated with different concentrations of Trichostatin A (TSA) and Rosiglitazone (ROZ) respectively to select the best combination through assessing cell proliferation by MTT assay. Then cells were randomly divided into control group, TSA group, ROZ group, and combination group. Cell proliferation was detected by MTT assay after 48 h; cell invasion was detected by Boyden chamber invasion test. The mRNA levels of PPARgamma and matrix metalloproteinase-2 (MMP-2) were assessed by reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of MMP-2 was evaluated by Western blot.


RESULTS
Both TSA and ROZ inhibited the proliferation of SGC-7901 cells in a dose-dependent manner. A combination of 20 nmol/L TSA and 5 mumol/L ROZ synergistically inhibited the invasion of SGC-7901 cells (q=1.41). ROZ down-regulated the mRNA and protein expression of MMP-2. TSA and ROZ in combination reduced MMP-2 expression more obviously than ROZ alone. TSA up-regulated the expression of PPARgamma mRNA.


CONCLUSIONS
HDAC suppresses the activation of PPARgamma through a series of molecular mechanisms. The activity of ROZ in inhibiting invasion of human gastric carcinoma cells can be enhanced after the activity of HDAC is inhibited by TSA.
Ma
Guo-Dong
GD
Department of General Surgery, First Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Zhang
Cai-Quan
CQ
Hou
Jun
J
Zhang
Long-Yun
LY
Lin
Chao
C
D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000077154:Rosiglitazone; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; C012589:trichostatin A; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D006655:Histone Deacetylases