Platycodin D inhibits glioblastoma cell proliferation, migration, and invasion by regulating DEPDC1B-mediated epithelial-to-mesenchymal transition.

BACKGROUND: Platycodin D (PD) is a potent bioactive constituent in the medicinal herb Platycodon grandiflorum. It has shown anticancer properties, particularly against glioblastoma (GB) and other human malignancies. DEPDC1B (DEP domain-containing protein 1B) is an oncogene associated with epithelial-mesenchymal transition (EMT). It is highly expressed in GB and correlated with tumor grade and patient prognosis. In this study, we investigated whether the antiglioma effect of PD was associated with downregulation of DEPDC1B. METHODS: Gene expression and clinical data were obtained from the China Glioma Genome Atlas and The Cancer Genome Atlas databases for glioma samples. In vitro experiments were conducted using Cell Counting Kit-8 and Transwell assays to assess the impact of PD on the proliferation, migration, and invasion of GB cells. mRNA and protein expression was evaluated using real-time polymerase chain reaction and western blotting, respectively. RESULTS: PD exerted inhibitory effects on the proliferation and motility of GB cells. PD downregulated DEPDC1B protein as well as several markers associated with EMT, namely N-cadherin, vimentin, and Snail. The suppressive effects of PD were enhanced when DEPDC1B was knocked down in GB cells, while overexpression of DEPDC1B in cells reversed the inhibitory effects of PD. CONCLUSION: PD exerts an antiglioma effect by regulating DEPDC1B-mediated EMT.

Platycodin D suppresses proliferation, migration, and invasion of human glioblastoma cells through regulation of Skp2.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: PD suppresses glioma development by regulation of Skp2 in GBM cells.

Clinicopathological and prognostic significance of long non-coding RNA EWSAT1 in human cancers: A review and meta analysis.

BACKGROUND: Ewing sarcoma-associated transcript 1 (lncRNA EWSAT1) is reported to have a close relationship with the overall survival in many cancers. However, the role of its prognosis and correlations with the clinicopathological features in different cancers haven't been explored yet. Herein, we intend to assess the prognostic value and correlations with the clinicopathological features in several cancers. METHODS: PubMed, Embase, Web of Science, and The Cochrane Library were searched for literature review from inception to October 25, 2021. Valid data was extracted to make forest and sensitivity analysis plots using Review Manager 5.4 and Stata software. Hazard ratio (HR) or odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship between different expression of EWSAT1 and patients' prognosis and clinicopathological features. RESULTS: 7 studies were screened for this review, including 550 samples. Meta-analysis showed that high expression of lncRNA EWSAT1 was associated with poor overall survival (OS) (HR = 2.10, 95% CI, 1.60-2.75, p < 0.0001) in cancers reported. In addition, patients in high expression group of EWAST1 tended to have more metastasis (OR = 2.20, 95% CI 1.47-3.31, p = 0.0001), and higher TNM stage (I+II vs. III: OR = 0.34, 95% CI 0.21-0.56, p < 0.0001), but in the same time with higher differentiation (well + moderate vs. Poor: OR = 2.21, 95% CI 1.02-4.76, p = 0.04). Age (OR = 1.47, 95% CI 0.94-2.30, p = 0.09) was not significantly different in patients with aberrant expression of EWSAT1. CONCLUSIONS: Our study shows that high expression of EWSAT1 may indicate poor overall survival and associated with several clinicopathological features, which can be used as a potential prognosis biomarker for multiple cancers.