Roles Of An Autophagy/Lysosomal Pathway In NF-κB Pathway Blocked Pancreatic Cancer Panc-1 Cells

Objective: To investigate the expression and biological significance of associated proteins in nuclear factor-kappa B signal transduction pathway in pancreatic ductal adenocarcinoma(PDAC); To study the roles of an autophagy / lysosomal pathway in NF-κB pathway blocked pancreatic cancer Panc-1 cells.Methods: The expressions of NF-κB/p65, IκBαand IKKβwere determined by tissue microarray and immunohistochemistry(IHC) in pancreatic carcinoma tissue and normal pancreatic tissue. The relationship between their expressions and the clinicopathologic parameters, the survival time of the patients were analyzed. The MTT assay was used to determine the cytotoxic effects of SN50. The expression of autophagy was monitored with monodansylcadaverin(MDC) staining, LC3 immunofluorescence and Transmission Electron Microscope(TEM) after SN50 treatment. Molecular mechanism was determined by using Western blotting analysis.Results: The positive rates of NF-κB/p65 and IKKβin pancreatic cancer tissue were higher than that in normal pancreatic tissue, but the positive rate of IκBαis opposite. Positive rates were closely correlated to TNM clinical stage and metastasis. The aberrant expressions of NF-κB/p65, IκBαand IKKβwere significantly related to short survival. The inhibitor of NF-κB p65 nuclear translocation inhibited the growth of cells, activated the autophagy and promoted autophagic cell death. It indicated that the inhibitor of NF-κB p65 upregulated the expressions of autophagy specific protein LC3 and autophagy-related protein Beclin1, reduced the expression of p62 protein and enhanced the expression of p53 and IκBα.Conclusion: NF-κB signal transduction pathway plays an important role in occurrence and development of pancreatic carcinoma. It can provide new evidences for the earlier diagnosis of pancreatic carcinoma and prognosis by using tissue microarray to detect certain proteins in NF-κB signal transduction pathway. The inhibitor of NF-κB p65 nuclear translocation activated autophagy and induced autophagic cell death in pancreatic cancer Panc-1 cell line.