Anlotinib inhibits the development of esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway

Background: Anlotinib, a small molecule multi-targeted tyrosine kinase inhibitor, is widely used in the treatment of various diseases. This study aimed to investigate the potential therapeutic effects and possible molecular mechanisms of anlotinib on esophageal squamous cell carcinoma (ESCC) . Methods: : Cell viability was detected by CCK-8 assay. Wound-healing and transwell assay were used to evaluate the migratory-invasive ability of ESCC cells. Apoptosis was detected by Hoechst33342 fluorescence staining. Transcript data were obtained by RNA sequencing. Transcript data were analyzed for differentially expressed genes (DEGs) using the DESeq2 program. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed using R package clusterProfiler. Western blotting was used to detect the protein expression level. Results: : The results of functional experiments showed that anlotinib can inhibit the viability of KYSE30 cells with time- and dose-dependent toxicity. The IC50 at 24h, 48h and 72h were 124.85μM, 21.226μM and 13.03μM, respectively. Anlotinib also inhibited cell migration and invasion, and induced apoptosis. Transcriptome sequencing results showed that anlotinib resulted in 359 genes were up-regulated and 156 down-regulated in KYSE30 cells. GO analysis of these DEGs showed that GO mainly included biological processes and molecular functions. KEGG enrichment analysis showed that PI3K/AKT pathway was the most critical signaling pathway. Western blot demonstrated that anlotinib inhibited the phosphorylation of AKT , and the total protein expression of PI3K and AKT . Conclusion: Anlotinib inhibits the progression of ESCC cells by modulating the PI3K / AKT signaling pathway.