Fig. 1: Mechanistic validation of a vicious accumulation between cisplatin and p53.

a Kaplan-Meier plot of the correlation between the mutation of p53 and the survival of patients with NSCLC (Log-rank Mantel–Cox test). Cisplatin (Cis), fluvastatin (Flu). b Outline of the assays of cisplatin treatment (low dose, 10 μM; moderate (mod) dose, 25 μM; high dose, 50 μM). Cholesterol (Cho). Heatmap of the number of mutations and RNA-seq analysis (c), ROS levels (d), Cho levels (e), and DNA damage (f) for wtp53-expressing cells treated with cisplatin for 30 days. g High-throughput sequencing before and after fluvastatin sodium (4 μM) treatment in A549 cells. h Genome-wide analysis. The volcano plot depicts the significance and magnitude of difference (Fold Change). The dashed line indicates the threshold of the Fold Change > 2 and adjusted p < 0.05. Some of the cancer related genes are labeled by dark colors. i GO enrichment analysis of differentially expressed genes (DEGs). The advanced bubble chart shows GO enrichment of DEGs in signaling pathways. The x-axis label represents the gene ratio, and the y-axis label represents GO terms. j GSEA analysis. The normalized enrichment scores (NES) and p values are indicated in each plot. k Heatmap analysis of mevalonate pathway genes from RNA-seq data. The color scale indicates the fold change in genes expression. l Schematic illustration of treatment with cisplatin. b, g created with BioRender.com. Data are shown as the mean ± SD; n.s. = no significance. Source data are provided as a Source Data file.