Fractalkine/CX3CR1 Induces Apoptosis Resistance And Proliferation Through The Activation Of The AKT/NF-?B Cascade In Pancreatic Cancer Cells

Background:Pancreatic cancer is one of the most lethal gastrointestinal tract malignancies and the fourth most common cause of cancer-related death worldwide.The overall prognosis for patients diagnosed with pancreatic cancer remains dismal,with 5-year survival rates averaging<6%.Cancer cells are difficult to eliminate because of the unlimited growth and proliferation,transformation and metastasis of cancer cells.But till now,the exact mechanism of occurrence and development is still not clear.Objective:The aim of this study was to explore the role of FKN on the proliferation and apoptosis in pancreatic cancer cell;and explore the physiological mechanism of FKN affecting the proliferation and apoptosis in pancreatic cancer cells.So we find FKN/CX3CRlassociated with tumor progression and prognosis,which will provide the effective targeted for cancer therapy.Methods:In this study,we detected the expression levels of FKN and CX3CR1 by immunohistochemistry in fresh pancreatic cancer and paracarcinoma tissues which obtained from 25 patients who were verified by surgery and pathology diagnosis.We chose three pancreatic cancer cell lines Capan-2,MIA PaCa-2,Aspc-1.We detected the expression of FKN and CX3CR1 in pancreatic cancer cell lines.By western blotting,CCK-8,flow cytometry,immunofluorescence and other techniques we tested the effects of FKN plasmid,exogenous FKN and FKN small interfering RNAs on pancreatic cancer cell proliferation,apoptosis and cell cycle.Finally,we studied the physiological mechanism of FKN in the process of proliferation and apoptosis of pancreatic cancer by the inhibitors of PI3K and NF-kappa B/p65.Results:FKN and CX3CR1 have expressed in pancreatic cancer and paracarcinoma tissues,and the expression levels of them were all higher in carcinoma tissues than that in paracarcinoma tissues.In the pancreatic cancer cell Capan-2,MIA PaCa-2 and Aspc-1,FKN and CX3CR1 were also highly expressed by Western Blotting.the results of flow cytometry,immune fluorescent confocal experiment and western blotting showed that FKN can promote pancreatic cancer cell proliferation and inhibit apoptosis of pancreatic cancer cells and promote cell cycle G1 phase to S phase.However,this effect was significantly reduced after the addition of PI3K or NF-kappa B/p65 inhibitors.Conclusion:The study confirmed that FKN combined with its receptor CX3CR1 can promote pancreatic cancer cell proliferation and inhibit apoptosis through the AKT/NF-kappaB/p65 signal pathway,which influenced the development of pancreatic cancer.The above results indicate that FKN/CX3CR1 may be an effective target for early treatment of pancreatic cancer.