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Objective:To investigate the expression of forkhead box protein O3(FOXO3) in pancreatic cancer and its effect on the motility and proliferation of pancreatic cancer cells.Methods:The FOXO3 expression in pancreatic cancer and adjacent tissues was retrieved from LinkedOmics database. Western blotting and real-time quantitative polymerase chain reaction were used to detect FOXO3 expression in pancreatic cancer cells and human pancreatic stellate cells. PANC-1 and MIAPaCa-2 pancreatic cancer cells with low FOXO3 expression were selected to transfect FOXO3 overexpression plasmid and negative control plasmid, respectively. The motility and proliferation ability of pancreatic cancer cells were detected by colony formation assay, cell scratch assay, Transwell assay and flow cytometry.Results:In the LinkedOmics database, the relative expression of FOXO3 protein in the cancer tissues of 64 patients with pancreatic cancer was significantly lower than that in the adjacent tissues ( t=8.36, P<0.001). The number of clones in PANC-1 cell line was (30.0±6.6) after overexpressed FOXO3, which was lower than that in negative control cells (92.7±6.7), and the difference was statistically significant ( t=11.54, P<0.001). After overexpressed FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the scratch repair rate was significantly decreased compared with the control group. In Transwell experiment, the number of cells in FOXO3 overexpressed group in PANC-1 cell lines was (21.0±6.6), which was lower than that of negative control groups (55.7±8.5), and the difference was statistically significant ( t=5.59, P=0.005). The results of MIAPaCa-2 cell line were consistent with that of PANC-1 cell line. After overexpressing of FOXO3 in PANC-1 and MIAPaCa-2 cell lines, the proportion of cells in the G0/G1 phase decreased, while the proportion in the S phase increased. Conclusion:The expression of FOXO3 was decreased in pancreatic cancer. Overexpression of FOXO3 could significantly inhibit the proliferation, migration and invasion of pancreatic cancer cells and induce cell cycle arrest, which is a potential target for the treatment of pancreatic cancer.
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Objective:To study the impact and the mechanism of splenectomy combined with pericardial devascularization on cirrhotic livers.Methods:Serum samples and clinical data were collected preoperatively and postoperatively from 54 patients with cirrhosis who underwent splenectomy combined with pericardial devascularization from May 2013 to Oct 2014 at Beijing You’an Hospital, Capital Medical University. Changes in hepatic arterial and portal venous blood flow, liver function and fibroscan results were analyzed. The levels of nitric oxide (NO), endothelin-1 (ET-1), interleukin-6 (IL-6), hepatocyte growth factor (HGF), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase 1 (MMP1) were measured.Results:There were 31 males and 23 females, aged(45.48±10.21)years. Free portal vein pressure decreased significantly from (37.0±7.1) cmH 2O (1 cmH 2O=0.098 kPa) to (26.1±5.7) cmH 2O after surgery ( P<0.05). Significant increases in postoperative lumen diameter (4.0±1.0) mm vs (3.1±0.7) mm were observed, accompanied by increase in peak flow velocity and blood flow of the hepatic artery. Significant deductions in lumen diameter (11.9±2.0) mm vs (13.1±1.9) mm, accompanied by reduction of peak flow velocity and blood flow of the portal vein were observed following surgery (all P<0.05). The NO level was significantly elevated immediately after splenectomy and was subsequently remained at high levels. The ET-1 level decreased 2 days after surgery and became fluctuated at low levels. The IL-6 and HGF levels increased significantly 2 days after surgery and decreased gradually after 7 days and 1 month, respectively. The TGF-β1 and the MMP1 levels increased after surgery. The endotoxin level decreased significantly after surgery (all P<0.05). Conclusion:Splenectomy combined with pericardial devascularization induced hepatic blood flow restoration, hepatocyte regeneration and reversal of fibrosis in cirrhotic livers. Splenectomy has a protective effect on cirrhotic liver when combined with pericardial devascularization.
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Objective:To investigate the expression of IKBKE and NF-κB in pancreatic cancer, and to explore the effect of IKBKE on pancreatic cancer proliferation and migration.Methods:Immunohistochemistry staining was used to study the expression of IKBKE and NF-κB in tissues of 61 pancreatic cancer patients admitted to the Second Hospital of Tianjin Medical University from January 2012 to January 2017 and 13 normal pancreatic tissues. The correlations between those expression to clinicopathological features were analyzed. Lentivirus mediated RNAi was transfected into pancreatic cancer cells to block IKBKE. Western blot was performed to test the silencing effeciency; CCK-8 and plate clone and scratch assays were used to investigate the proliferation and migration of pancreatic cancer.Results:Immunohistochemical staining showed that 60 (98.4%) of IKBKE staining were weakly positive, positive, and strongly positive in pancreatic cancer tissues, which were significantly higher than normal pancreatic tissues(76.9% cases were weakly positive and the rest were negative), and the differences were statistically significant ( P<0.05). All cases of NF-κB exhibited weakly positive expression and above in pancreatic cancer tissues, which was markedly higher than normal tissues (30.8% cases were weak positive and the rest were negative staining), statistically significant ( P<0.05). Survival analysis showed that patients with high level of IKBKE showed a shorter overall survival ( P<0.05). CCK-8, plate cloning and scratch assays showed that the proliferation and migration of were significantly decreased in IKBKE knocking down group ( P<0.05). Conclusions:IKBKE and NF-κB are highly expressed in pancreatic cancer, and IKBKE is correlated with NF-κB in pancreatic cancer. Blocking of IKBKE could distinctly inhibit the proliferation and migration of pancreatic cancer.
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Patients with liver fibrosis and cirrhosis experience certain changes in spleen morphology and function, and there is always a controversy over whether to perform splenectomy in patients with liver cirrhosis. As a surgical treatment of recurrent portal hypertension complicated by esophagogastric variceal bleeding, splenectomy can reduce portal venous pressure, reduce the possibility of gastrointestinal bleeding, and correct the reduced white blood cell count and platelet count. It can also protect the liver by improving liver function, promoting regeneration of hepatocytes, and inhibiting the progression of liver fibrosis. With reference to available clinical and laboratory data, this article reviews the effect of splenectomy on the cirrhotic liver and related issues such as selection of surgical procedures and prevention and treatment of postoperative complications, in order to promote splenectomy in patients with liver cirrhosis.