[6]-Paradol suppresses proliferation and metastases of pancreatic cancer by decreasing EGFR and inactivating PI3K/AKT signaling

Abstract Background The underlying mechanism behind the tumorigenesis and progression of pancreatic cancer is not clear, treatment failure generally caused by early metastasis, recurrence, drug resistance vascular invasion. Exploring novel therapeutic regimens necessary to overcome improve patients outcomes. Methods Functional assays were performed investigate role [6]-Paradol (6-P) in proliferation metastasis vitro vivo. interaction between EGFR 6-P was tested KEGG enrichment analysis molecular docking analysis. qRT-PCR detect mRNA expression treated groups. Involvement PI3K/AKT pathway measured western blotting. Results significantly suppressed cell metastasis. suggested that there existed certain 6-P. In addition, obviously decreased protein level but did change EGFR. could induce degradation through decreasing stability enhancing ubiquitin-mediated proteasome-dependent degradation, 6-P-mediated led inactivation signaling pathway. However, ectopic resulted inactivity inhibition malignant phenotype cancer. Inversely, erlotinib enhance anticancer activity. Conclusion Our data indicated 6-P/EGFR/PI3K/AKT axis might become one potential therapies for