Abstract
Objective. To investigate the effects of Cyclocarya paliurus polysaccharide (CPP) on the proliferation, migration, invasion, and apoptosis of human glioma U251 cells and further explore the underlying mechanism. Methods. U251 cells were cultured in vitro and treated with various concentrations (25, 50, 75, 100, 125, and 150 μmol/L) of CPP for 24, 48, and 72 h. Cell counting kit-8 was used to detect the activity of cell proliferation. Wound-healing assay, Transwell assay, and flow cytometry were used to measure the effects of CPP on the migration, invasion, and apoptosis of U251 cells, respectively. Western blotting was used to determine the protein expression involved in the GSK3β/β-catenin signaling pathway and its downstream genes related to proliferation, migration, invasion, and apoptosis including Cyr61, CCND1, Vimentin, and Slug. Meanwhile, qRT-PCR was used to detect the mRNA levels of Cyr61, CCND1, Vimentin, and Slug. Results. We found that CPP not only could inhibit the proliferation, migration, and invasion of U251 cells but also promote its apoptosis in vitro. Besides, CPP could significantly inhibit the phosphorylation and decrease the protein levels of GSK3 β at ser9 site (p<0.05), and thus increasing the phosphorylation of β-Catenin at ser33/37 site (p<0.05), resulting in β-Catenin degradation. In addition, we also found that CPP could downregulate the mRNA (p<0.05) and protein expression (p<0.05) of downstream genes of GSK3 β/β-catenin signaling pathway including Cyr61, CCND1, Vimentin, and Slug, which are related to proliferation, migration, invasion, and apoptosis. Conclusion. CPP could inhibit the expression of GSK3β, promote the degradation of β-catenin, and downregulate the levels of GSK3β/β-catenin downstream genes including Cyr61, CCND1, Vimentin, and Slug, which regulate the proliferation, migration, invasion, and apoptosis of glioma cells.
Highlights
Glioma is one of the most aggressive malignant brain cancers, accounting for approximately 36% of primary brain tumors [1]
The results suggest that the administration of Cyclocarya paliurus polysaccharide (CPP) to U251 cells can induce the occurrence of apoptotic responses
This study found that CPP can play a positive role in the treatment of gliomas by inhibiting the activation of GSK3β/β-catenin signaling pathway and inhibiting the downstream gene expression related to proliferation, apoptosis, migration, and invasion
Summary
Glioma is one of the most aggressive malignant brain cancers, accounting for approximately 36% of primary brain tumors [1]. Glioma originates from glial cells and accounts for about 80% of malignant tumors of the central nervous system [2]. Gliomas have a lower incidence than other cancers, gliomas have a relatively high mortality rate due to their highly invasive growth characteristics [3]. Despite the advances in treatment over the past decade, there is still no effective cure [4]. Chemotherapy is an important method for the treatment of gliomas. It can kill residual tumors that cannot be removed by surgery and radiotherapy. It is of great significance to research the antiglioma drugs
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