Growth inhibition of mesenchymal stem cells by aspirin: involvement of the WNT/beta-catenin signal pathway.
1. Mesenchymal stem cell (MSC) therapy is drawing increasing attention in cardiology. However, the effect of aspirin, an assistant medication used extensively in the treatment of cardiovascular diseases, on MSC is not clear. 2. In the present study, we investigated the effect of aspirin on the growth of MSC in vitro and the underlying mechanism of its action. 3. The 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay revealed that 1, 5 and 10 mmol/L aspirin inhibited the growth of MSC by 18, 37 and 62%, respectively. DNA synthesis of MSC was inhibited by 25, 57 and 90% following treatment with 1, 5 and 10 mmol/L aspirin, respectively, as determined by the tritiated thymidine incorporation assay. No cytotoxicity was observed based on Trypan blue dye exclusion and cell morphological observations. Western blot analysis demonstrated that the protein level of phosphorylated beta-catenin increased, whereas that of cyclin D1 decreased, after treatment of MSC with aspirin. Cell cycle analysis showed that aspirin failed to significantly alter the proportion of cells in different stages of the cell cycle. 4. These observations indicate that aspirin inhibits MSC proliferation and that the downregulation of the wnt/beta-catenin signal pathway may be involved in the growth inhibition of MSC by aspirin.
Wang
Yiner
Y
Research Center for Cardiovascular Regenerative Medicine, Cardiovascular Institute , Beijing, China.
Chen
Xi
X
Zhu
Weiquan
W
Zhang
Hao
H
Hu
Shengshou
S
Cong
Xiangfeng
X
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D051153:Wnt Proteins; D051176:beta Catenin; D019938:Cyclin D1; D001241:Aspirin