Fig. 4

CLDN1 is a key mediator to oxaliplatin resistance in CRC cell lines (A) CLDN1 membrane expression in oxaliplatin-resistant cell lines and their parental cell lines. Top: Immunofluorescence images of CLDN1 membrane expression in SW620-ROX cells (oxaliplatin resistant) and in SW620 cells (parental line). (B) Effect of CLDN1 silencing (shCLDN1) on oxaliplatin IC50 in the two oxaliplatin-resistant cell lines incubated with oxaliplatin compared with the shLUC controls. (C) Five GSEA hallmarks deregulated after oxaliplatin treatment with significantly enriched genes in SW620_ROX–shCLDN1 and -shLUC cells. Dot plots indicate the gene ratios (number of core genes over the total number of genes in the set). Dots are colored in function of the adjusted p-value and their size in the gene set. (D) Enrichment plots for the apoptosis hallmark. The location of the gene set members is indicated by vertical black lines and showed a significant positive enrichment (left) in SW620_ROX–shCLDN1 cell samples compared with SW620_ROX-shLUC samples (E) FACS profiles of annexin V-APC/7-AAD staining in the two oxaliplatin-resistant cell lines in which CLDN1 was silenced (-shCLDN1) or not (-shLUC) and incubated or not with oxaliplatin (5µM for 24 h). Apoptosis was quantified in at least three experiments (Student’s t-test)