c-Myc downregulation: a critical molecular event in resveratrol-induced cell cycle arrest and apoptosis of human medulloblastoma cells
c-Myc downregulation: a critical molecular event in resveratrol-induced cell cycle arrest and apoptosis of human medulloblastoma cells
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DOI：
10.1007/s11060-006-9172-7
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发表时间：
2006-05
影响因子：
3.9
通讯作者：
P. Zhang;Hong Li;Mo-li Wu;Xiao-yan Chen;Qing-you Kong;Xiao-Wei Wang;Yuan Sun;S. Wen;Jia Liu
中科院分区：
文献类型：
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作者：
P. Zhang;Hong Li;Mo-li Wu;Xiao-yan Chen;Qing-you Kong;Xiao-Wei Wang;Yuan Sun;S. Wen;Jia Liu
本研究通过检测(1)c-Myc在髓母细胞瘤组织和细胞系（UW228-2和UW228-3）中的表达，(2)白藜芦醇对c-Myc体外表达的影响，(3)c-Myc抑制对细胞生长和存活的影响，探讨c-Myc表达与白藜芦醇诱导髓母细胞瘤细胞更新的相关性。人髓母细胞瘤和非癌性小脑组织的免疫组化染色显示，11例肿瘤组织中有8例（72.7%）表达c-Myc，其中4例（50%）显示核标记增强。RT-PCR、Western blotting、免疫细胞化学和免疫荧光染色显示c-Myc下调，并伴有生长抑制和凋亡。流式细胞术分析显示白藜芦醇处理的细胞群S相阻滞。在培养的髓母细胞瘤细胞中转染c-Myc定向反义寡核苷酸可降低c-Myc的表达，抑制细胞生长，使细胞周期停留在S期。因此，我们的研究结果首次证明了c-Myc下调是白藜芦醇介导的抗髓母细胞瘤活性的一个关键分子事件，它与髓母细胞瘤细胞的生长抑制、细胞周期阻滞和凋亡密切相关。
The correlation of c-Myc expression with resveratrol-induced turnover of medulloblastoma cells was investigated in this study by checking (1) c-Myc expression in medulloblastoma tissues and cell lines (UW228-2 and UW228-3), (2) the in vitro effect of resveratrol on c-Myc expression and (3) the influences of c-Myc inhibition in cell growth and survival. Immunohistochemical staining of human medulloblastomas and noncancerous cerebellar tissues revealed that 8 out of 11 tumor tissues (72.7%) expressed c-Myc, in which 4 cases (50%) showed intensified nuclear labeling. RT-PCR, Western blotting, immunocytochemical and immunofluorescence stainings revealed c-Myc downregulation accompanied with growth suppression and apoptosis. Flow cytometry analysis showed S phase arrest in resveratrol-treated cell populations. Transfection of c-Myc directed antisense oligonucleotides to the cultured medulloblastoma cells could reduce c-Myc expression, inhibit cell growth and arrest the cell cycle at S phase. Our results thus for the first time demonstrate that c-Myc downregulation is a critical molecular event of resveratrol-mediated anti-medulloblastoma activity, which is closely associated with growth suppression, cell cycle arrest and apoptosis of medulloblastoma cells.