脑膜瘤作为中枢神经系统肿瘤的一种,常因局部扩张而压迫神经中枢,进一步引起神经功能缺损。然而,脑膜瘤的治疗方法有限。ITF2357 是一种有效的 I 类和 II 类组蛋白脱乙酰酶抑制剂 (HDACi),已被证明可抑制细胞增殖,促进细胞凋亡,并阻断各种肉瘤细胞的细胞周期,包括胶质母细胞瘤和外周 T 细胞淋巴瘤。在这里,我们研究了 ITF2357 对脑膜瘤癌细胞(IOMM-Lee 细胞)的潜在作用。首先,我们通过 MTT 测定证明了 ITF2357 的半数最大抑制浓度 (IC50) 为 1.842 μM。此外,ITF2357 有效抑制了 IOMM-Lee 细胞的增殖和定植能力。流式细胞术分析表明,ITF2357 诱导 G0/G1 和 G2/M 期细胞周期停滞和细胞凋亡。从机械上讲,RNA 测序数据显示 ITF2357 可以影响 PI3K-Akt 信号通路和细胞周期进程。此外,通过蛋白质印迹法测定 Akt、PI3K、p-Akt 和 p-PI3K 的表达水平。总的来说,我们的数据显示,ITF2357 通过抑制 PI3K-Akt 通路的过度激活,诱导 G0 G1 和 G2/M 期阻滞和细胞凋亡,最终抑制脑膜瘤细胞的细胞活力和增殖,从而开发出治疗脑膜瘤的新方法。p-Akt 和 p-PI3K 通过蛋白质印迹法测定。总的来说,我们的数据显示,ITF2357 通过抑制 PI3K-Akt 通路的过度激活,诱导 G0 G1 和 G2/M 期阻滞和细胞凋亡,最终抑制脑膜瘤细胞的细胞活力和增殖,从而开发出治疗脑膜瘤的新方法。p-Akt 和 p-PI3K 通过蛋白质印迹法测定。总的来说,我们的数据显示,ITF2357 通过抑制 PI3K-Akt 通路的过度激活,诱导 G0 G1 和 G2/M 期阻滞和细胞凋亡,最终抑制脑膜瘤细胞的细胞活力和增殖,从而开发出治疗脑膜瘤的新方法。
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ITF2357 induces cell cycle arrest and apoptosis of meningioma cells via the PI3K-Akt pathway
As a type of central nervous system tumor, meningioma usually compresses the nerve center due to its local expansion, further causing neurological deficits. However, there are limited therapeutic approaches for meningiomas. ITF2357, a potent class I and II histone deacetylase inhibitor (HDACi), has been shown to inhibit cell proliferation, promote apoptosis, and block the cell cycle in various sarcoma cells, including glioblastoma and peripheral T-cell lymphoma. Here, we investigated the potential role of ITF2357 on meningioma cancer cells (IOMM-Lee cells). First, we demonstrated that the half-maximal inhibitory concentration (IC50) of ITF2357 was 1.842 μM by MTT assay. In addition, ITF2357 effectively inhibited the proliferation and colonization ability of IOMM-Lee cells. Flow cytometry analysis showed that ITF2357 induced G0/G1 and G2/M phase cell cycle arrest and cell apoptosis. Mechanically, the RNA sequencing data revealed that ITF2357 could affect the PI3K-Akt signaling pathway and the cell cycle progression. Furthermore, the expression levels of Akt, PI3K, p-Akt, and p-PI3K were determined by western blotting. Collectively, our data revealed that ITF2357 induces G0 G1 and G2/M phase arrest and apoptosis by inhibiting hyperactivation of the PI3K-Akt pathway, ultimately inhibiting cell viability and proliferation of meningioma cells, which developed a new approach to the treatment of meningioma.