Fig. 3: ER stress is involved in Osimertinib-induced paraptosis.
From: Osimertinib induces paraptosis and TRIP13 confers resistance in glioblastoma cells

A Volcano plot of differentially expressed genes (DEGs) in Osimertinib-treated LN-229 and vehicle-treated control cells (left panel). The upregulated genes (UP) were depicted by red points (corrected p-value < 0.05, log2Fold-Change > 1). The downregulated genes (DOWN) were depicted by blue points (corrected p-value < 0.05, log2Fold-Change < −1). The pink points stand for genes that were not significantly differentially expressed (NOT). Reactome pathway enrichment analysis for upregulated genes (right panel). Top 10 enriched pathways were shown. The x-axis represents the corrected p-value, the number of genes mapping to the corresponding enriched pathways was labeled in parentheses. Representative genes belonging to the highest-ranking pathway (unfolded protein response (UPR)) were highlighted. The heatmap shows the per-row mean centered gene expression log2 (FPKM + 1) values for UPR genes. B, C LN-229 and U87MG cells were exposed to Osimertinib (5 μM) in the absence or presence of Salubrinal (5 μM), 4 μ8C (2.5 μM), ISRIB (2.5 μM) for 24 h. Cell lysates were analyzed by immunoblotting (IB) using the indicated antibodies (B) and cell morphology was examined by phase-contrast microscopy (C) (scale bar = 20 μm). The numbers of vacuolated and non-vacuolated cells were counted manually, and the ratio of vacuolated cells was calculated and shown as mean ± SD, n = 6; **p < 0.01, ***p < 0.001. D GBM cells (LN-229-shcon, LN-229-shCHOP, U87MG-shcon, U87MG-shCHOP) were vehicle-treated or treated with Osimertinib (5 μM) for 24 h. Cell lysates were analyzed by IB using the indicated antibodies. E LN-229 and U87MG cells were treated the same as in B, and cell growth was determined by CCK-8 cell survival assay. The results were shown as mean ± SD, n = 6; **p < 0.01. Data represent three independent experiments with similar results.