Department of Neuro-oncology & Neurosurgery, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
Neurochem Res. 2012 Oct;37(10):2076-84. doi: 10.1007/s11064-012-0828-8. Epub 2012 Jun 16.
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.
神经胶质瘤是中枢神经系统最恶性的肿瘤之一。作为过氧化物酶体增殖物激活受体γ（PPAR-γ）的激动剂，噻唑烷二酮（TZDs）可诱导广泛的肿瘤细胞生长停滞和细胞死亡。在本研究中，我们研究了罗格列酮在神经胶质瘤细胞中的作用。我们发现，罗格列酮作为 TZDs 的一员，抑制人神经胶质瘤细胞系 U87 和 U251 的生长。罗格列酮还诱导细胞周期停滞和细胞凋亡，这可能是其抗增殖作用的机制。接下来，我们发现罗格列酮抑制 TGF-β及其受体 TGF-βR2 的表达，并抑制 Smad3 的磷酸化。罗格列酮还抑制 Smad3/Smad4 复合物的形成。此外，罗格列酮影响与 Smad3/Smad4 相关的基因表达调节剂的表达，包括 p21 和 c-Myc。这些结果表明，罗格列酮通过阻断 TGF-β 介导的途径抑制人神经胶质瘤细胞的生长和细胞周期。
