Deoxypodophyllotoxin inhibits cell viability and invasion by blocking the PI3K/Akt signaling pathway in human glioblastoma cells (Retracted article. See vol. 50, 2023)
Deoxypodophyllotoxin inhibits cell viability and invasion by blocking the PI3K/Akt signaling pathway in human glioblastoma cells (Retracted article. See vol. 50, 2023)
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DOI：
10.3892/or.2019.7016
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发表时间：
2019-04-01
期刊：
影响因子：
4.2
通讯作者：
Bao, Yijun
中科院分区：
文献类型：
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作者：
Wang, Wei;Gao, Wei;Bao, Yijun
脱氧鬼臼毒素(DPT)是一种天然化学物质，已被证明在各种类型的癌细胞中抑制细胞的存活和运动。尽管先前的研究表明DPT抑制胶质瘤的发展与细胞程序性死亡和细胞周期停滞有关，但其潜在的机制尚未得到充分的探讨。用不同的方法阐明了DPT抑制胶质瘤细胞恶性行为的机制。用四甲基偶氮唑盐比色法检测细胞存活率。免疫印迹分析和逆转录定量聚合酶链式反应分别检测相关蛋白和mRNA的表达水平。流式细胞仪检测细胞周期分布和细胞凋亡率。用Hochest 33258染色检测细胞凋亡率。用Transwell分析方法分别评估无Matrigel和有Matrigel时的迁移能力和侵袭能力。DPT通过靶向磷脂酰肌醇4，5-二磷酸3-激酶(PI3K)/Rac-α丝氨酸/苏氨酸蛋白激酶(Akt)-细胞周期蛋白依赖性激酶抑制物1-细胞周期蛋白依赖性激酶2/细胞周期蛋白E信号通路，使细胞周期停滞于G1/S期，从而抑制细胞活力。此外，DPT通过减弱PI3K/Akt介导的对细胞死亡相关激动剂Bcl2表达的抑制而显著促进细胞凋亡，同时伴随着凋亡调节因子Bax/凋亡调节因子Bcl2比率的增加。此外，DPT还通过抑制PI3K/Akt-基质金属蛋白酶(MMP9)/MMP2信号通路而下调胶质瘤细胞的侵袭力。综上所述，DPT能有效抑制PI3K的表达，下调PI3K/Akt介导的信号通路，从而阻止胶质母细胞瘤的发展。
Deoxypodophyllotoxin (DPT) is a natural chemical that has been demonstrated to inhibit cellular viability and motility in various cancer cell types. Although previous studies have indicated that programmed cell death and cell cycle arrest are involved in the suppression of glioma development by DPT, the underlying mechanism has not been fully explored. Different methods were used to the elucidate the mechanisms of DPT that inhibit the malignant behavior of glioma cells. Cellular viability was assessed by MTT assay. Relative protein and mRNA expression levels were detected by western blot analysis and reverse transcription-quantitative polymerase chain reaction analyses, respectively. Cell cycle distribution and the apoptosis rate were detected by flow cytometry. Hochest 33258 staining was also performed to detect apoptosis. Transwell assays without and with Matrigel were used to assess migration and invasion abilities, respectively. It was determined that DPT suppressed cellular viability by inducing cell cycle arrest at the G1/S phase by targeting the phosphatidylinositol 4,5-bisphosphate 3-kinase (PI3K)/RAC-alpha serine/threonine-protein kinase (Akt)-cyclin-dependent kinase inhibitor 1-cyclin-dependent kinase 2/cyclin E signaling cascades. Additionally, DPT significantly enhanced apoptosis by attenuating the PI3K/Akt-mediated suppression of Bcl-2-associated agonist of cell death expression, which was accompanied by an increased apoptosis regulator BAX/apoptosis regulator Bcl-2 ratio. Furthermore, DPT downregulated the invasiveness of glioma cells by hindering PI3K/Akt-matrix metalloproteinase (MMP)9/MMP2 signaling pathways. In conclusion, DPT effectively inhibited the expression of PI3K and downregulated PI3K/Akt-mediated signaling pathways to prevent glioblastoma progression.