Rosiglitazone suppresses glioma cell growth and cell cycle by blocking the transforming growth factor-beta mediated pathway.
Glioma is one of the most malignant tumors in the central nervous system. As a peroxisome proliferator-activated receptor γ (PPAR-γ) activator, the thiazolidinediones (TZDs) induce growth arrest and cell death in a broad spectrum of tumor cells. In this study, we investigated the role of rosiglitazone in glioma cells. We found that rosiglitazone, a member of TZDs, suppresses growth of human glioma cell lines U87 and U251. Rosiglitazone also induces cell cycle arrest and apoptosis, which may be the mechanism of its anti-proliferation effect. Next, we found that rosiglitazone suppresses the expression of TGF-beta and its receptor TGF-betaR2, and suppresses phosphorylation of Smad3. Rosiglitazone also inhibits formation of the Smad3/Smad4 complex. Furthermore, Rosiglitazone affects the expression of Smad3/Smad4 associated regulators of gene expression, including p21 and c-Myc. These results suggest that rosiglitazone suppresses growth and cell cycle of human glioma cells by blocking the TGF-beta mediated pathway.
Department of Neuro-oncology & Neurosurgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Peng
P
Wang
Jinpu
J
Yu
Qiang
Q
Yin
Wenliang
W
Li
Xiubao
X
Ren
Xishan
X
Hao
D015153:Blotting, Western; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005910:Glioma / Q000473:pathology*; D006801:Humans; D010766:Phosphorylation; D000077154:Rosiglitazone; D051900:Smad3 Protein / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors*
C497790:SMAD3 protein, human; D051900:Smad3 Protein; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D000077154:Rosiglitazone