Ivermectin inhibits the growth of glioma cells by inducing cell cycle arrest and apoptosis in vitro and in vivo
Ivermectin inhibits the growth of glioma cells by inducing cell cycle arrest and apoptosis in vitro and in vivo
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伊维菌素通过在体外和体内诱导细胞周期停滞和细胞凋亡来抑制神经胶质瘤细胞的生长。
DOI：
10.1002/jcb.27420
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Gao, Aili
中科院分区：
文献类型：
--
作者：
Song, Dandan;Liang, Hongsheng;Gao, Aili
神经胶质瘤是最主要的原发性恶性脑肿瘤，由于缺乏有效的治疗方法，至今仍未治愈。因此，开发成功的治疗药物势在必行。本研究旨在探讨伊维菌素（IVM）对胶质瘤细胞的体外和体内抗肿瘤作用及其机制。采用MTT法/集落形成法、流式细胞术和透射电镜分别检测IVM对细胞活力、细胞周期阻滞、凋亡率和形态学特征的影响。Western blot检测细胞周期相关蛋白和凋亡相关蛋白的表达水平。此外，通过TUNEL、Ki-67、cleaved caspase-3和cleaved caspase-9免疫染色法进行细胞增殖和凋亡分析。我们的研究结果表明，IVM对胶质瘤细胞的凋亡率具有潜在的剂量依赖性抑制作用。同时，结果还显示IVM通过上调caspase-3和caspase-9活性，上调p53和Bax的表达，下调Bcl-2，激活裂解型caspase-3和裂解型caspase-9，下调CDK2、CDK4、CDK6、cyclin D1、这些研究结果表明，IVM在体外和体内通过触发细胞周期阻滞和诱导细胞凋亡，对胶质瘤细胞的增殖有抑制作用，可能是治疗胶质瘤的有希望的药物。
Glioma, the most predominant primary malignant brain tumor, remains uncured due to the absence of effective treatments. Hence, it is imperative to develop successful therapeutic agents. This study aimed to explore the antitumor effects and mechanisms of ivermectin (IVM) in glioma cells in vitro and in vivo. The effects of IVM on cell viability, cell cycle arrest, apoptosis rate, and morphological characteristics were determined respectively by MTT assay/colony formation assay, flow cytometry, and transmission electron microscope. In addition, the expression levels of cycle-related and apoptosis-associated proteins were individually examined by Western blot analysis. Moreover, cell proliferation and apoptosis analyses were carried out by TUNEL, Ki-67, cleaved caspase-3, and cleaved caspase-9 immunostaining assay. Our results demonstrated that IVM has a potential dosage-dependent inhibition effect on the apoptosis rate of glioma cells. Meanwhile, the results also revealed that IVM induced apoptosis by increasing caspase-3 and caspase-9 activity, upregulating the expressions of p53 and Bax, downregulating Bcl-2, activating cleaved caspase-3 and cleaved caspase-9, and blocking cell cycle in G0/G1 phase by downregulating levels of CDK2, CDK4, CDK6, cyclin D1, and cyclin E. These findings suggest that IVM has an inhibition effect on the proliferation of glioma cells by triggering cell cycle arrest and inducing cell apoptosis in vitro and in vivo, and probably represents promising agent for treating glioma.