Identification of the anti-cancer effect of silencing of LRP5 in glioblastoma cells

Glioblastoma (GBM) is a malignant brain tumor exhibiting aggressive behavior. The Wnt/β-catenin signaling pathway plays a critical role in the development of GBM tumors. This study aims to identify the potential anti-cancer effects following the suppression of Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5) expression, a component of the Wnt/β-catenin signaling pathway, in GBM and human brain cancer stem cell (BCSC) cells. Additionally, the anti-cancer effects after the Temozolomide (TMZ) treatment with the suppression of LRP5 expression were examined. The study was conducted on U87MG, T98G, and BCSC lines. In these cell lines, LRP5 expression was silenced via siRNAs. Following the silencing process, changes in the mRNA and protein expression levels of LRP5, Wnt/β-catenin pathway targets, and G0/G1 cell cycle regulatory genes were identified using quantitative PCR (qPCR) and Western Blot methods, respectively. The cell proliferation after silencing and/or TMZ treatment were examined using the Cell Viability Detection Kit 8 (CVDK-8) assay. The DNA fragmentation test was used to determine the effects of the treatments on apoptosis. The effects of suppressed LRP5 expression and/or TMZ on colony formation and invasion capacities were identified using wound healing and clonogenic assays. After the silencing process, the expression levels of LRP5 and target genes of the Wnt/β-catenin pathway decreased in GBM and BCSC cells. Similarly, a decrease was observed in the expression levels of genes regulating the G0/G1 phase of the cell cycle. Suppression of LRP5 in GBM and BCSC cells not only reduced cell proliferation but also increased the anti-proliferative effect when combined with TMZ. Suppression of LRP5 expression alone and in combination with TMZ significantly reduced the invasive properties of GBM and BCSC cells. The results indicate that suppressed LRP5 expression exerts an anti-cancer effect in GBM and BCSC cells and that TMZ efficacy may be enhanced when LRP5 is suppressed. LRP5 could be a promising therapeutic target for GBM treatment.