JSI-124 inhibits glioblastoma multiforme cell proliferation through G2/M cell cycle arrest and apoptosis augment
JSI-124 inhibits glioblastoma multiforme cell proliferation through G2/M cell cycle arrest and apoptosis augment
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JSI-124 通过 G2/M 细胞周期停滞和细胞凋亡增强抑制多形性胶质母细胞瘤细胞增殖。
DOI：
10.4161/cbt.7.8.6263
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发表时间：
2008-08-01
影响因子：
3.6
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Su, Yuhang;Li, Gang;Zhang, Jian
JSI-124 (cucurbitacin I) 是 Janus 激酶/信号转导器和转录激活剂 3 (JAK/STAT3) 的选择性抑制剂，已被证明在体外和体内均具有抗增殖和抗肿瘤特性。由于 STAT3 激活与胶质瘤的发生有关，我们通过干扰 STAT3 通路研究了 JSI-124 对多形性胶质母细胞瘤 (GBM) 的治疗效果。在本研究中，使用 JSI-124 处理两种 GBM 细胞系 U251 和 A172 细胞。结果表明，细胞生长受到显着抑制，且呈剂量和时间依赖性。进一步的研究表明，JSI-124 处理的 GBM 细胞中磷酸化 STAT3 的水平降低，同时细胞凋亡增加和细胞周期停滞。特别是，JSI-124 通过下调细胞周期蛋白 B1 和 cdc2 表达诱导 G(2)/M 积累。这些结果共同表明，JSI-124 抑制 STAT3 是开发新型多形性胶质母细胞瘤治疗药物的潜在策略。
JSI-124 (cucurbitacin I) is a selective inhibitor of Janus kinase / Signal transducer and activator of transcription 3(JAK/STAT3) and has been shown to exert anti-proliferative and anti-tumor properties both in vitro and in vivo. As STAT3 activation has been implicated in the development of glioma, we investigated the therapeutic efficacy of JSI-124 on glioblastoma multiforme (GBM) by interfering with STAT3 pathway. In present study, two GBM cell lines, U251 and A172 cells, were treated with JSI-124. The results showed that the cell growth was inhibited significantly in a dose-and time-dependent manner. Further investigation illustrated that the levels of phosphorylated-STAT3 were decreased in GBM cells treated by JSI-124, concomitant with apoptosis augment and cell cycle arrest. Specially, JSI-124 induced G(2)/M accumulation via downregulation of cyclin B1 and cdc2 expression. Together these results suggested that inhibition of STAT3 by JSI-124 is a potential strategy for the development of the new glioblastoma multiforme theraputics.