People's Clinical Medical College Affiliated to Nanchang University, Nanchang, 330006, People's Republic of China; Department of Neurosurgery, Jiangxi Provincial People's Hospital, Nanchang, 330006, People's Republic of China.
Department of Neurosurgery, Peking University People's Hospital, Beijing, 100044, People's Republic of China.
Eur J Pharmacol. 2023 Jun 5;948:175697. doi: 10.1016/j.ejphar.2023.175697. Epub 2023 Mar 29.
Platycodin D (PD) is a major bioactive component of Platycodon grandiflorum, a medicinal herb that is widely used in China, and is effective against various human cancers, including glioblastoma multiforme (GBM). S phase kinase-related protein 2 (Skp2) is oncogenic and overexpressed in various human tumors. It is highly expressed in GBM and its expression is correlated with tumor growth, drug resistance and poor prognosis. In this study, we investigated whether inhibition of glioma progression by PD is mediated by decreasing expression of Skp2.
Cell Counting Kit-8 (CCK-8) and Transwell assays were used to determine the effects of PD on GBM cell proliferation, migration, and invasion in vitro. mRNA and protein expression were determined by real time polymerase chain reaction (RT-PCR) and western blotting, respectively. The U87 xenograft model was used to verify the anti-glioma effect of PD in vivo. Expression levels of Skp2 protein were analyzed by immunofluorescence staining.
PD suppressed proliferation and motility of GBM cells in vitro. The expression of Skp2 in U87 and U251 cells was significantly reduced by PD. PD mainly decreased the cytoplasmic expression of Skp2 in glioma cells. Skp2 protein expression was downregulated by PD, resulting in upregulation of its downstream targets, p21and p27. The inhibitory effect of PD was enhanced by Skp2 knockdown in GBM cells and reversed in cells with Skp2 overexpression.
PD suppresses glioma development by regulation of Skp2 in GBM cells.
桔梗皂苷 D (PD) 是桔梗的主要生物活性成分，桔梗是一种在中国广泛使用的药用植物，对多种人类癌症有效，包括多形性胶质母细胞瘤 (GBM)。S 期激酶相关蛋白 2 (Skp2) 是致癌基因，在各种人类肿瘤中过度表达。它在 GBM 中高度表达，其表达与肿瘤生长、耐药性和预后不良相关。在这项研究中，我们研究了 PD 是否通过降低 Skp2 的表达来抑制神经胶质瘤的进展。
使用细胞计数试剂盒-8 (CCK-8) 和 Transwell 测定法来确定 PD 对 GBM 细胞体外增殖、迁移和侵袭的影响。通过实时聚合酶链反应 (RT-PCR) 和蛋白质印迹分别确定 mRNA 和蛋白质表达。使用 U87 异种移植模型来体内验证 PD 的抗神经胶质瘤作用。通过免疫荧光染色分析 Skp2 蛋白的表达水平。
PD 抑制了 GBM 细胞在体外的增殖和迁移。PD 显著降低了 U87 和 U251 细胞中 Skp2 的表达。PD 主要降低了神经胶质瘤细胞中 Skp2 的细胞质表达。PD 下调 Skp2 蛋白表达，导致其下游靶标 p21 和 p27 的上调。在 GBM 细胞中 Skp2 敲低增强了 PD 的抑制作用，而 Skp2 过表达逆转了这种作用。
PD 通过调节 GBM 细胞中的 Skp2 抑制神经胶质瘤的发展。
