EFFECT OF LENVATINIB ON THE AUTOPHAGY AND MIGRATION OF CANCER-ASSOCIATED FIBROBLASTS IN HEPATOCELLULAR CARCINOMA TISSUE

Abstract

Objective To investigate the effect of lenvatinib on the autophagy and migration of cancer-associated fibroblasts (CAFs) in hepatocellular carcinoma (HCC) tissue. Methods Primary CAFs from HCC patients were isolated and cultured and were then treated with an equal volume of DMSO (DMSO group) or 46 nmol/L lenvatinib (lenvatinib group) for 72 h. Transcriptomic sequencing and the omics analysis of drug targets were performed for the two groups, and GO functional enrichment analysis and KEGG pathway enrichment analysis were performed for differentially expressed genes and peptides. Transmission electron microscopy was used to observe the effect of lenvatinib on autophagy of CAFs, and Transwell assay and wound hea-ling assay were used to observe the effect of lenvatinib on the migration ability of CAFs. Results The differentially expressed genes and peptides between the DMSO group and the lenvatinib group were mainly enriched in the functions and pathways such as cell migration and autophagy. Transmission electron microscopy showed that the lenvatinib group had a significantly higher number of autophagosomes than the DMSO group (t=5.376,P<0.05), and Transwell assay and wound healing assay showed that the lenvatinib group had a significantly weaker migration ability than the DMSO group (t=10.31,14.33,P<0.05). Conclusion Lenvatinib can induce the autophagy of CAFs and inhibit their migration in HCC tissue.

Keywords

• carcinoma, hepatocellular|lenvatinib|cancer-associated fibroblasts|cell movement|autophagy|in vitro techniques