目的从细胞水平和分子水平探讨榄香烯对胶质瘤细胞的作用机制。方法取胶质细胞瘤的U251细胞株做体外培养，四甲基偶氮唑盐比色（MTT）法检测榄香烯对人神经胶质瘤细胞U251的增生抑制作用，流式细胞术（FCM）检测细胞周期、细胞内钙离子（IECa^2＋）含量、Fas、bcl-2、增生细胞核抗原（PCNA）蛋白表达及细胞凋亡。结果榄香烯能有效抑制胶质瘤细胞U251的恶性增生，MTT法检测榄香烯处理不同时间（24、48、72h）的半数生长抑制剂量（IC50），24、48、72h其IC50分别为40．60、38．14、34．35μg／ml。经榄香烯作用后，细胞周期可阻滞在S期和G2／M期。用异硫氰酸胍荧光素（Annexin V FITC）染色检测发现细胞凋亡率明显增加。榄香烯还可下调PCNA、Fas蛋白的表达，上调细胞内Ca^2＋（IECa^2＋）含量，对bcl-2蛋白表达无显著影响。结论榄香烯有显著的抗胶质瘤细胞增生作用，并能通过下调PCNA蛋白的表达，上调细胞内Ca^2＋含量，诱导细胞凋亡，对Fas表达也有影响，可能与bcl-2基因表达无关。
Astrocyte elevated gene-1 (AEG-1) was cloned as an human immunodeficiency virus -1-inducible and tumor necrosis factor-α-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. AEG-1 down-regulates the expression of the glutamate transporter EAAT2,thus,it is implicated in glutamate-induced excitotoxic damage to neurons as evident in HIV-associated neurodegeneration. Meanwhile,AEG-1 expression is elevated in subsets of breast cancer,prostatic cancer,glioblastoma multiforme and melanoma cells,having a dual specificity phosphatase activity. Overexpression of AEG-1 increases and siRNA inhibition of AEG-1 decreases migration and invasion of human glioma cells,respectively. Recent observations indicate that AEG-1 exerts its effects by activating the nuclear factor kappa B (NF-κB) pathway and AEG-1 is a downstream target of Ha-ras and plays an important role in Ha-ras-mediated tumorigenesis. These findings are intensifying interest in AEG-1 as a crucial regulator of tumor progression and metastasis and as a potential mediator of neurodegeneration.
