School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.
Int J Biol Macromol. 2020 Aug 1;156:471-484. doi: 10.1016/j.ijbiomac.2020.03.243. Epub 2020 Mar 31.
Glioblastoma (GBM) is the most malignant central nervous system tumor, with poor prognosis. Temozolomide (TMZ) has been used as a first-line drug for the treatment of GBM for over a decade, but its treatment benefits are limited by acquired resistance. Polysaccharides from Cibotium barometz (CBPs) are polysaccharides purified from the root of Cibotium barometz (L.) J. Sm., possessing sensitizing activity. The purpose of this study was to investigate the anti-cancer effect of CBP from different processing methods on U87 cells using a H NMR-based metabolic approach, complemented with qRT-PCR and flow cytometry, to identify potential markers and discover the targets to explore the underlying mechanism. Cibotium barometz is usually processed under sand heating in clinical applications. Polysaccharides from both the processed (PCBP) and raw (RCBP) C. barometz were prepared, and the effect on enhancing the sensitivity to TMZ was investigated in vitro. CBP can significantly increase the toxicity of TMZ to the U87 cell line, promote apoptosis, enhance cell cycle changes, and arrest cells in S phase, and RCBP demonstrated better activity. Multivariate statistical analyses, such as principal component analysis (PCA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA), were used to identify metabolic biomarkers, and 12 metabolites in the cell extract samples were clearly identified as altered after RCBP exposure. NMR-based cell metabolomics provided a holistic method for the identification of CBP's apoptosis-enhancing mechanisms and the exploration of its potential applications in preclinical and clinical studies.
胶质母细胞瘤（GBM）是最恶性的中枢神经系统肿瘤，预后不良。替莫唑胺（TMZ）已被用作治疗 GBM 的一线药物超过十年，但由于获得性耐药，其治疗效果有限。从叉叶苏铁（Cibotium barometz）中提取的多糖（CBPs）是从叉叶苏铁（L.）J. Sm.的根部提取的多糖，具有致敏活性。本研究旨在使用基于 H NMR 的代谢方法，结合 qRT-PCR 和流式细胞术，研究不同加工方法的 CBP 对 U87 细胞的抗癌作用，以鉴定潜在标志物并发现目标，以探讨其潜在机制。叉叶苏铁在临床应用中通常采用沙加热法进行加工。制备了加工（PCBP）和生（RCBP）叉叶苏铁的多糖，并在体外研究了它们对 TMZ 增敏作用的影响。CBP 能显著增加 TMZ 对 U87 细胞系的毒性，促进细胞凋亡，增强细胞周期变化，使细胞停滞在 S 期，RCBP 表现出更好的活性。多元统计分析，如主成分分析（PCA）和正交偏最小二乘判别分析（OPLS-DA），用于鉴定代谢标志物，RCBP 暴露后细胞提取物样本中的 12 种代谢物明显改变。基于 NMR 的细胞代谢组学为鉴定 CBP 促凋亡机制提供了一种整体方法，并为其在临床前和临床研究中的潜在应用提供了探索。
