Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, PR China.
Oncol Rep. 2011 Aug;26(2):405-13. doi: 10.3892/or.2011.1276. Epub 2011 Apr 20.
β-elemene, a natural drug extracted from Curcuma wenyujin, strongly inhibits glioblastoma growth. However, the mechanism of β-elemene antitumor action remains unclear. Glia maturation factor β (GMFβ) regulates cellular growth, fission, differentiation and apoptosis. It has been reported that overexpression of GMFβ inhibits the growth of glioblastoma cells and decreases tumor volume. To illustrate the role of GMFβ in the anti-proliferative effect of β-elemene in glioblastoma, U87 cells were treated with β-elemene at various doses and for different periods of time, and levels of phospho-GMFβ (p-GMFβ) and total GMFβ were determined by immunoprecipitation and western blot analysis. Upon GMFβ silencing using RNA interference, the antitumor action of β-elemene was evaluated in a methyl thiazolyl tetrazolium assay and by semi-quantitative western blot analysis of MKK3/6 and p-MKK3/6 expression. Finally, chemosensitization to cisplatin by β-elemene was examined using a cell counting array, and the cell growth inhibitory rate was calculated. The results showed that β-elemene inhibits U87 cell viability through the activation of the GMFβ signaling pathway. Conversely, silencing the expression of GMFβ reversed the antitumor effect of β-elemene and impaired the phosphorylation of MKK3/6. Furthermore, β-elemene increased the sensitivity of U87 glioblastoma cells to the chemotherapeutic agent cisplatin. Taken together, these results suggest that activation of the GMFβ pathway mediates the antitumor effect of β-elemene in glioblastoma. GMFβ is a putative molecular target for glioblastoma therapy.
β-榄香烯是从莪术中提取的天然药物,强烈抑制神经胶质瘤的生长。然而,β-榄香烯抗肿瘤作用的机制尚不清楚。胶质细胞成熟因子β(GMFβ)调节细胞的生长、分裂、分化和凋亡。有报道称,GMFβ的过表达抑制神经胶质瘤细胞的生长,减少肿瘤体积。为了说明 GMFβ在β-榄香烯抑制神经胶质瘤增殖中的作用,用不同剂量的β-榄香烯处理 U87 细胞不同时间,并通过免疫沉淀和 Western blot 分析测定磷酸化 GMFβ(p-GMFβ)和总 GMFβ的水平。用 RNA 干扰沉默 GMFβ后,通过噻唑蓝比色法和半定量 Western blot 分析 MKK3/6 和 p-MKK3/6 的表达来评估β-榄香烯的抗肿瘤作用。最后,通过细胞计数阵列检测β-榄香烯对顺铂的化疗增敏作用,并计算细胞生长抑制率。结果表明,β-榄香烯通过 GMFβ信号通路的激活抑制 U87 细胞活力。相反,沉默 GMFβ 的表达逆转了β-榄香烯的抗肿瘤作用,并损害了 MKK3/6 的磷酸化。此外,β-榄香烯增加了 U87 神经胶质瘤细胞对化疗药物顺铂的敏感性。综上所述,这些结果表明 GMFβ 通路的激活介导了β-榄香烯在神经胶质瘤中的抗肿瘤作用。GMFβ 是神经胶质瘤治疗的潜在分子靶点。