α-茄碱通过调节细胞凋亡-自噬轴抑制胶质母细胞瘤多形性生长和转移特性

A. Cuschieri, Byron Baron
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摘要

摘要:多形性胶质母细胞瘤(GBM)虽经最佳治疗,但预后较差。最近的研究表明植物化学物质作为抗癌剂的潜力。α-龙葵碱是从茄属植物中提取的,是一种很有前途的分子。研究α-龙葵碱与替莫唑胺(TMZ)对GBM细胞株(U87MG、U251和T98G)的体外抗氧化作用。方法:采用体外实验方法,比较α-龙葵碱对U87MG、U251和T98G GBM细胞株的活性、迁移、侵袭及细胞死亡方式。通过Rt-qPCR和蛋白质组学分析在分子水平上研究α-龙葵碱诱导的变化。结果:α-龙葵碱对所有GBM细胞系均表现出较强的细胞毒性,IC50值在19.66µM ~ 22.87µM之间,与TMZ处理相比,α-龙葵碱显著抑制GBM细胞的迁移。RNA和蛋白水平分析显示凋亡和自噬蛋白均上调,表明BECN1和BNIP3L参与α-茄碱诱导的细胞死亡。讨论与结论:这些发现有助于寻找有效的GBM治疗方法。未来的研究应增加生物重复的数量,采用替代方法来加强研究结果,并利用患者来源的GBM组织进行体内实验和测试,以更好地评估α-龙葵碱对GBM的治疗适用性,并充分了解α-龙葵碱对GBM的作用模式。
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α-Solanine Suppresses Glioblastoma Multiforme Growth and Metastatic Properties by Modulating the Apoptosis-autophagy Axis
Introduction: Glioblastoma multiforme (GBM) has a poor prognosis despite optimal treatment. Recent studies have shown the potential of phytochemicals as anti-cancer agents. α-solanine, derived from plants of the Solanum genus, is a promising molecule in this regard. This study investigated the efficacy of α-solanine compared to temozolomide (TMZ) against GBM cell lines (U87MG, U251, and T98G) in vitro. Methods: In-vitro assays were conducted to assess the viability, migration, invasion, and mode of cell death of U87MG, U251 and T98G GBM cell lines following α-solanine treatment in comparison to TMZ. Rt-qPCR and proteome profiling were conducted to investigate the changes induced by α-solanine on a molecular level. Results: α-solanine demonstrated potent cytotoxicity on all GBM lines, with IC50 values ranging from 19.66 µM to 22.87 µM between cell lines tested, and significantly inhibited GBM cell migration compared to TMZ treatment. RNA and protein level assays indicated upregulation of both apoptotic and autophagy proteins, suggesting the involvement of BECN1 and BNIP3L in α-solanine-induced cell death. Discussion and Conclusion: These findings contribute to the search for effective GBM treatments. Future studies should increase the number of biological replicates, employ alternative methods to strengthen the findings, and conduct in vivo experiments and testing using patient-derived GBM tissue to better evaluate any therapeutic suitability of and fully understand the mode of action of α-solanine on GBM.
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