Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Huan-Qi Zhang, Dao-Ming Zhang, Zhi-Zhen Huang, Jing Cheng, Chong Zhang, Neng-Ming Lin, Yangling Li
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引用次数: 0

Abstract

Glioblastoma multiforme (GBM) presents a significant challenge in oncology due to its highly aggressive nature and inherent resistance to conventional therapeutic interventions. Vortioxetine, a novel antidepressant, exhibits anticancer abilities and can traverse the blood-brain barrier. In this study, the antitumor effect and mechanism of vortioxetine on GBM cells were investigated. Cell proliferation in GBM cells was assessed using the CCK8 and colony formation assays. Flow cytometry, western blot, and wound healing assay were used to study the mechanisms of vortioxetine. mCherry-GFP-LC3B and confocal microscopy were used to evaluate autophagic activity. RNA sequencing uses the capabilities of high-throughput sequencing methods to provide insight into the transcriptome of cells. Vortioxetine significantly inhibited the proliferation of GBM cells by inducing G1/G0 phase cell cycle arrest. Meanwhile, it also reduced the migratory capabilities of GBM cells. Furthermore, it promoted apoptotic cell death in GBM cells. In addition, it promoted autophagy in GBM cells, and autophagy inhibitors markedly enhanced its antiproliferative activities. Vortioxetine could down-regulate the expressions of PI3K and Akt, which were related to the occurrence and development of GBM. Our findings support the potential of vortioxetine as a novel therapeutic agent for GBM treatment. Vortioxetine exhibits anti-GBM activity via the PI3K-Akt signaling pathway. Meanwhile, our findings reveal autophagy inhibitors as an effective sensitizer for vortioxetine, offering new strategies for treating GBM.

Vortioxetine通过PI3K-Akt信号通路显示抗胶质母细胞瘤活性。
多形性胶质母细胞瘤(GBM)由于其高度侵袭性和对传统治疗干预的固有抗性,在肿瘤学领域提出了重大挑战。Vortioxetine是一种新型抗抑郁药,具有抗癌能力,可以穿过血脑屏障。本研究探讨沃替西汀对GBM细胞的抗肿瘤作用及其机制。使用CCK8和集落形成试验评估GBM细胞的细胞增殖。采用流式细胞术、western blot和创面愈合实验研究沃替西汀的作用机制。使用mCherry-GFP-LC3B和共聚焦显微镜评估自噬活性。RNA测序使用高通量测序方法的能力来提供对细胞转录组的洞察。Vortioxetine通过诱导G1/G0期细胞周期阻滞显著抑制GBM细胞的增殖。同时也降低了GBM细胞的迁移能力。此外,它还能促进GBM细胞凋亡。此外,它还能促进GBM细胞的自噬,自噬抑制剂显著增强其抗增殖活性。Vortioxetine可下调与GBM发生发展相关的PI3K和Akt的表达。我们的研究结果支持vortioxetine作为治疗GBM的新药物的潜力。Vortioxetine通过PI3K-Akt信号通路显示抗gbm活性。同时,我们的研究结果表明,自噬抑制剂作为沃替西汀的有效增敏剂,为治疗GBM提供了新的策略。
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来源期刊
Iranian Journal of Basic Medical Sciences
Iranian Journal of Basic Medical Sciences MEDICINE, RESEARCH & EXPERIMENTAL-PHARMACOLOGY & PHARMACY
CiteScore
4.00
自引率
4.50%
发文量
142
审稿时长
6-12 weeks
期刊介绍: The Iranian Journal of Basic Medical Sciences (IJBMS) is a peer-reviewed, monthly publication by Mashhad University of Medical Sciences (MUMS), Mashhad, Iran . The Journal of "IJBMS” is a modern forum for scientific communication. Data and information, useful to investigators in any discipline in basic medical sciences mainly including Anatomical Sciences, Biochemistry, Genetics, Immunology, Microbiology, Pathology, Pharmacology, Pharmaceutical Sciences, and Physiology, will be published after they have been peer reviewed. This will also include reviews and multidisciplinary research.
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