青蒿琥酯抑制人头颈部鳞状细胞癌增殖及诱导凋亡的机制.

Objective To study the influence of artesunate (Akt) on the proliferation and apoptosis of human head and neck squamous cell carcinoma (HNSCC), and to explore its molecular mechanism thereof. Methods The HNSCC cell line, UM-SCC-10A cells, was cultured in vitro. The Inhibitory concentration 50 (IC50) was examined by MTT assay. The cell morphological changes were observed under inverted light micro-scope after being interfered by 0, 2.5, 5, 10, 20 and 40μmol/L Akt. Cell cycle changes and apoptosis were measured by flow cytometry. And the expression of cell cycle regulators and apoptotic associated protein were detected by Western blot assay. Results MTT assay demonstrated that Akt significantly inhibited the proliferation of UM-SCC-10A cells in dose-dependent manner. After UM-SCC-10A cells were treated with Akt for 48 h, IC50 was 15.01μmol/L. Morphological changes of cell apoptosis such as karyopyknosis and conglomeration were ob?served by Hoechst 33258 staining. Flow cytometry showed that the apoptosis was associated with cell cycle arrest during the G1 phase. Western blot analysis showed that p53 and p21 protein was up-regulated and Cyclin D protein was down-regulated. Furthermore, results revealed that Bcl-2 associated X protein induced by a mitochondrial pathway, cytochrome C and caspase-3 were up-regulated, and Bcl-2 and procaspase-3 were down-regulated. The mitochondrial membrane potential was reduced. Conclusion Artesunate can induce apoptosis of UM-SCC-10A cells via a mitochondrial pathway, which was associated with cell cycle arrest in the G1 phase. As a result, artesunate has an obvious inhibitory effects on proliferation of UM-SCC-10A cells. [ABSTRACT FROM AUTHOR]