Fig. 1

Upregulated PPP in regorafenib-resistant cells. A Colony formations were detected on drug-sensitive and regorafenib-resistant cells and cells were treated with or without regorafenib for 48 h, n = 3. B Half maximal inhibitory concentration (IC₅₀) of regorafenib performed on drug-sensitive and regorafenib-resistant cells and cells were treated with gradient concentration of regorafenib for 24 h, n = 3. C Apoptosis plot diagram(left) and apoptosis rate(right) were detected by FCM and cells were treated with regorafenib for 24 h. D The differential metabolites that displayed significantly different abundances between drug-sensitive (Huh7) and regorafenib-resistant cells (Huh7-RR) were subjected for KEGG analysis. The vertical axis represents top metabolic pathways and the horizontal axis represents the importance value of pathways. n = 8. E The metabolic network of potential biomarkers. Upregulated substances were colored with red; downregulated substances were colored with blue; undetected substances were colored with black. IMP, Hypoxanthine-9-β-D-Arabinofuranoside; AMP, Adenosine monophosphate; PRPP, Phosphoribosyl pyrophosphate; UMP, Uridine monophosphate; dTMP, deoxythymidine monophosphate. F Protein (left, n = 3) and mRNA (right, n = 3) expression of PPP in Huh7 and Huh7-RR. G Protein (left, n = 3) and mRNA (right, n = 5) expression of PPP in Hep3B and Hep3B-RR. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001, mean ±SD