Protein and metabolic profiles of tyrosine kinase inhibitors co-resistant liver cancer cells
- Front Pharmacol. 2024 May 21:15:1394241. doi: 10.3389/fphar.2024.1394241.
- 1. Department of Immunology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
- 2. Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fujian Medical University, Fuzhou, China.
- 3. Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou, China.
- 4. Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
- 5. Department of Cadres's Healthcare Office, Fujian Provincial Hospital, Fuzhou, China.
- 6. Department of Hematology, Fujian Provincial Hospital, Fuzhou, China.
- # Contributed equally.
Hepatocellular Carcinoma (HCC) patients often develop resistance to tyrosine kinase inhibitors (TKIs) like sorafenib (SR) and lenvatinib (RR). We established HCC cell lines resistant to these drugs and analyzed the correlation between protein and metabolite profiles using bioinformatics. Our analysis revealed overexpression of MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1, and downregulation of IFITM3, CA4, AGR2, and SLC51B in drug-resistant cells. Differential signals are mainly enriched in steroid hormone biosynthesis, cell adhesion, and immune synapses, with metabolic pathways including Cytochrome P450 drug metabolism, amino acid metabolism, and glycolysis. Proteomics and metabolomics analysis showed co-enrichment signals in drug metabolism, Amino acids, glucose metabolism, Ferroptosis, and Other biological processes. Knocking down MISP, CHMP2B, IL-18, TMSB4X, and EFEMP1 significantly reduced drug resistance, indicating their potential as therapeutic response biomarkers. This study characterizes protein and metabolic profiles of drug-resistant HCC cells, exploring metabolite-protein relationships to enhance understanding of drug resistance mechanisms and clinical treatment.