The present study was designed to examine effects of Sinomenine (SM) on glioma cells growth in vivo and in vitro. Cells growth and apoptosis were detected by MTT assay, TUNEL assay and flow cytometric analysis. In the study, SM treatment led to growth inhibition on a series of glioma cell lines, including U87, U373, U251, Hs683 and T98G. SM prevented U87 growth in the nude mice as well. Inhibitory effects of SM on U87 cells proliferation in vitro and in vivo were more effective than that of temozolomide (TMZ), and SM has synergistic effects with TMZ in the glioma therapy. SM induced apoptotic death in U87 cells via activation of caspase-3, caspase-8 and caspase-9, and down-regulation of HIAP, Bcl-2 and survivin. Moreover, we observed SM decreased the expression of phosphorylated STAT3 (p-STAT3) both in vivo and in vitro. Interestingly, using a specific activator of STAT3, we demonstrated overexpression of p-STAT3 impaired, SM mediated growth inhibition and apoptosis induction in the U87 cells. In summary, our results indicate SM induced growth suppression of human glioma cells through inhibiting phosphorylation of STAT3.
- MeSH
- Alkaloids pharmacology therapeutic use MeSH
- Apoptosis genetics immunology drug effects MeSH
- Astrocytes drug effects MeSH
- Glioma drug therapy pathology ultrastructure MeSH
- Caspases analysis metabolism MeSH
- Cells, Cultured MeSH
- Cell Line, Tumor immunology metabolism drug effects MeSH
- Signal Transduction MeSH
- Sinomenium chemistry MeSH
- In Vitro Techniques MeSH
- STAT3 Transcription Factor antagonists & inhibitors metabolism drug effects MeSH