Belkaid Anissa, Copland Ian B, Massillon Duna, Annabi Borhane
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre BIOMED, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Que., Canada H3C 3P8.
FEBS Lett. 2006 Jun 26;580(15):3746-52. doi: 10.1016/j.febslet.2006.05.071. Epub 2006 Jun 9.
G6P translocase (G6PT) is thought to play a crucial role in transducing intracellular signaling events in brain tumor-derived cancer cells. In this report, we investigated the contribution of G6PT to the control of U-87 brain tumor-derived glioma cell survival using small interfering RNA (siRNA)-mediated suppression of G6PT. Three siRNA constructs were generated and found to suppress up to 91% G6PT gene expression. Flow cytometry analysis of propidium iodide/annexin-V-stained cells indicated that silencing the G6PT gene induced necrosis and late apoptosis. The anticancer agent curcumin, also inhibited G6PT gene expression by more than 90% and triggered U-87 glioma cells death. Overexpression of recombinant G6PT rescued the cells from curcumin-induced cell death. Targeting G6PT expression may provide a new mechanistic rationale for the action of chemopreventive drugs and lead to the development of new anti-cancer strategies.
葡萄糖-6-磷酸转运体（G6PT）被认为在转导脑肿瘤来源癌细胞的细胞内信号事件中起关键作用。在本报告中，我们使用小干扰RNA（siRNA）介导的G6PT抑制，研究了G6PT对U-87脑肿瘤来源的胶质瘤细胞存活控制的贡献。构建了三种siRNA构建体，发现其可抑制高达91%的G6PT基因表达。碘化丙啶/膜联蛋白-V染色细胞的流式细胞术分析表明，沉默G6PT基因会诱导坏死和晚期凋亡。抗癌剂姜黄素也可将G6PT基因表达抑制90%以上，并引发U-87胶质瘤细胞死亡。重组G6PT的过表达使细胞从姜黄素诱导的细胞死亡中获救。靶向G6PT表达可能为化学预防药物的作用提供新的机制原理，并导致新的抗癌策略的开发。
