Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
Environ Toxicol. 2024 Feb;39(2):562-571. doi: 10.1002/tox.23882. Epub 2023 Jul 14.
Glioma, a type of malignant brain tumor, has become a challenging health issue globally in recent years.
In this study, we investigated the potential therapeutic role of scoparone in glioma and the underlying mechanism. Initially, transcriptome sequencing was conducted to identify genes that exhibited differential expression in glioma cells treated with scoparone compared to untreated cells. Subsequently, the impact of scoparone on the proliferation, migration, and invasion of glioma cells was assessed in vitro using a range of assays including cell viability, colony formation, wound healing, and transwell assays. Moreover, the apoptotic effects of scoparone on glioma cells were evaluated through flow cytometry and western blot analysis. Furthermore, we established a glioma xenograft mouse model to assess the in vivo antitumor activity of scoparone. Lastly, by integrating transcriptome analysis, we endeavored to unravel the molecular mechanisms underlying the observed antitumor effects of scoparone by examining the expression levels of RhoA/ROCK1 signaling pathway components using western blot analysis and qRT-PCR.
Our transcriptome sequencing results revealed that scoparone significantly downregulated RhoA/ROCK1 signaling in glioma cells. Furthermore, scoparone treatment inhibited glioma cell proliferation, migration, and invasion, and promoted cell apoptosis in vitro. Moreover, scoparone reduced tumor growth and prolonged survival in a glioma xenograft mouse model, and improved the toxicity of temozolomide. Finally, our results showed that the antitumor effects of scoparone were mediated by the suppression of RhoA/ROCK1 signaling.
Scoparone could be a promising therapeutic agent for glioma by suppressing RhoA/ROCK1 signaling. These findings pave the way for future research endeavors aimed at the development and optimization of scoparone-based therapeutic strategies.
近年来，神经胶质瘤（一种恶性脑肿瘤）已成为全球范围内极具挑战性的健康问题。
在本研究中，我们研究了桉油精在神经胶质瘤中的潜在治疗作用及其潜在机制。首先，通过转录组测序，鉴定了桉油精处理与未处理的神经胶质瘤细胞之间差异表达的基因。随后，通过一系列实验，包括细胞活力、集落形成、划痕愈合和 Transwell 实验，评估了桉油精对神经胶质瘤细胞体外增殖、迁移和侵袭的影响。此外，通过流式细胞术和 Western blot 分析评估了桉油精对神经胶质瘤细胞的凋亡作用。进一步建立神经胶质瘤异种移植小鼠模型，评估桉油精的体内抗肿瘤活性。最后，通过整合转录组分析，我们通过 Western blot 分析和 qRT-PCR 检测 RhoA/ROCK1 信号通路成分的表达水平，研究桉油精观察到的抗肿瘤作用的分子机制。
我们的转录组测序结果表明，桉油精可显著下调神经胶质瘤细胞中的 RhoA/ROCK1 信号。此外，桉油精治疗可抑制神经胶质瘤细胞的增殖、迁移和侵袭，并促进细胞凋亡。此外，桉油精可减少神经胶质瘤异种移植小鼠模型中的肿瘤生长并延长生存期，并改善替莫唑胺的毒性。最后，我们的结果表明，桉油精的抗肿瘤作用是通过抑制 RhoA/ROCK1 信号介导的。
桉油精通过抑制 RhoA/ROCK1 信号，可能成为神经胶质瘤有前途的治疗剂。这些发现为进一步研究开发和优化桉油精为基础的治疗策略铺平了道路。
