XAV939, a tankyrase 1 inhibitior, promotes cell apoptosis in neuroblastoma cell lines by inhibiting Wnt/β-catenin signaling pathway.
XAV939, a tankyrase 1 inhibitior, promotes cell apoptosis in neuroblastoma cell lines by inhibiting Wnt/β-catenin signaling pathway.
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DOI：
10.1186/1756-9966-32-100
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发表时间：
2013-12-05
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Tian XH;Hou WJ;Fang Y;Fan J;Tong H;Bai SL;Chen Q;Xu H;Li Y
神经母细胞瘤（NB）是儿童时期最常见的颅外实体瘤。目前的治疗方法包括手术、化疗和放疗，长期治愈率只有40%，并且通常会导致肿瘤复发。因此，寻找新的有效且毒性较小的疗法具有重要意义。 XAV939 是坦科聚合酶 1 (TNKS1) 的小分子抑制剂。本研究的目的是探讨XAV939对NB细胞系增殖和凋亡的影响及其相关机制。在本研究中，我们使用XAV939治疗和RNAi方法来证明TNKS1抑制可能是治疗NB的潜在机制。 MTT 方法用于确定细胞活力和后续测定的适当浓度。集落形成实验、Annexin V染色和细胞周期分析用于检测集落形成能力、细胞凋亡和不同细胞周期的百分比。 Western blot检测Wnt/β-catenin（Wnt/β-catenin）信号通路关键蛋白的表达情况。结果表明，TNKS1抑制降低了SH-SY5Y、SK-N-SH和IMR-32细胞的活力，诱导SH-SY5Y和SK-N-SH细胞凋亡，并导致NB细胞在细胞周期的S和G2/M期积累。此外，我们证明 TNKS1 抑制可能部分阻断 Wnt/β-catenin 信号传导并减少抗凋亡蛋白的表达。最后，我们还证明了 TNKS1 抑制可减少体外集落形成。这些发现表明TNKS1可能是治疗NB的潜在分子靶点。
Neuroblastoma (NB) is the most common extracranial solid tumor in childhood. The present treatment including surgery, chemotherapy and radiation, which have only 40% long-term cure rates, and usually cause tumor recurrence. Thus, looking for new effective and less toxic therapies has important significance. XAV939 is a small molecule inhibitor of tankyrase 1(TNKS1). The objective of this study is to investigate the effect of XAV939 on the proliferation and apoptosis of NB cell lines, and the related mechanism. In the present study, we used both XAV939 treatment and RNAi method to demonstrate that TNKS1 inhibition may be a potential mechanism to cure NB. MTT method was used for determining the cell viability and the appropriate concerntration for follow-up assays. The colony formation assay, Annexin V staining and cell cycle analysis were used for detecting colony forming ability, cell apoptosis and the percentage of different cell cycle. The Western blot was used for detecting the expression of key proteins of Wnt/ beta-catenin (Wnt/β-catenin) signaling pathway. The results showed that TNKS1 inhibition decreased the viability of SH-SY5Y, SK-N-SH and IMR-32 cells, induced apoptosis in SH-SY5Y as well as SK-N-SH cells, and led to the accumulation of NB cells in the S and G2/M phase of the cell cycle. Moreover, we demonstrated TNKS1 inhibition may in part blocked Wnt/β-catenin signaling and reduced the expression of anti-apoptosis protein. Finally, we also demonstrated that TNKS1 inhibition decreased colony formation in vitro. These findings suggested that TNKS1 may be a potential molecule target for the treatment of NB.
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影响因子：
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