印楝叶提取物通过调节凋亡途径诱导人神经母细胞瘤异种移植瘤的放射增敏作用。
Neem leaf extract induces radiosensitization in human neuroblastoma xenograft through modulation of apoptotic pathway.
作者信息
Veeraraghavan Jamunarani, Aravindan Sheeja, Natarajan Mohan, Awasthi Vibhudutta, Herman Terence S, Aravindan Natarajan
机构信息
Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
出版信息
Anticancer Res. 2011 Jan;31(1):161-70.
UNLABELLED
Induction of apoptosis is directly correlated with the biological effectiveness of ionizing radiation (IR). Accordingly, we investigated the efficacy of neem leaf extract (NLE) on IR-associated apoptotic transcriptional modulation and cell death in neuroblastoma (NB).
MATERIALS AND METHODS
NB xenografts exposed to single dose (SDR, 10 Gy) or fractionated (FIR, 2 Gy/d×5d) with or without NLE were examined for transcriptional activation of 84 apoptotic pathway genes using quantitative polymerase chain reaction. Apoptosis was measured using TdT nick-end labeling.
RESULTS
FIR induced 55 and suppressed 10 genes, while SDR induced 49 and suppressed 5 genes. Of these, 46 and 4 genes were commonly up/down-regulated after FIR and SDR. NLE inhibited IR-induced NAIP, BIRC6, BIRC8, NOL3 and enhanced BAK1, BAX, BCL10, CASP1, CASP10 CARD8 and CRADD. Furthermore, NLE conferred FIR- and SDR-induced cell death.
CONCLUSION
These data imply that NLE may exert radiosensitization by activating pro-apoptotic signaling and negating survival signaling and may thus potentiate radiotherapy in NB.
未标记
细胞凋亡的诱导与电离辐射（IR）的生物学效应直接相关。因此，我们研究了印楝叶提取物（NLE）对神经母细胞瘤（NB）中IR相关的凋亡转录调节和细胞死亡的作用。
材料与方法
使用定量聚合酶链反应检测接受单剂量（SDR，10 Gy）或分次照射（FIR，2 Gy/d×5 d）且联合或不联合NLE的NB异种移植瘤中84个凋亡通路基因的转录激活情况。使用末端脱氧核苷酸转移酶介导的缺口末端标记法检测细胞凋亡。
结果
FIR诱导55个基因表达上调，抑制10个基因表达；SDR诱导49个基因表达上调，抑制5个基因表达。其中，FIR和SDR后分别有46个和4个基因共同上调/下调。NLE抑制IR诱导的NAIP、BIRC6、BIRC8、NOL3基因表达，并增强BAK1、BAX、BCL10、CASP1、CASP10、CARD8和CRADD基因表达。此外，NLE增强FIR和SDR诱导的细胞死亡。
结论
这些数据表明，NLE可能通过激活促凋亡信号和消除生存信号发挥放射增敏作用，从而增强NB的放射治疗效果。
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