Su Yuhang, Li Gang, Zhang Xulong, Gu Jinhai, Zhang Cai, Tian Zhigang, Zhang Jian
Department of Neurosurgery, Qilu Hospital of Shandong University, Jinan, Shandong, China.
Cancer Biol Ther. 2008 Aug;7(8):1243-9. doi: 10.4161/cbt.7.8.6263. Epub 2008 Aug 10.
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 therapeutics.
JSI-124（葫芦素I）是一种Janus激酶/信号转导子和转录激活子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发展有关，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，用JSI-124处理了两种GBM细胞系，U251和A172细胞。结果表明，细胞生长受到显著抑制，呈剂量和时间依赖性。进一步研究表明，JSI-124处理的GBM细胞中磷酸化STAT3水平降低，同时细胞凋亡增加和细胞周期停滞。特别地，JSI-124通过下调细胞周期蛋白B1和细胞分裂周期蛋白2（cdc2）的表达诱导G2/M期积累。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一种潜在策略。
