ABSTRACT
OBJECTIVE@#To investigate the simultaneous inhibition of X-linked inhibitor of apoptosis protein (XIAP) and survivin expression on epithelial-mesenchymal transition (EMT) and invasiion of pancreatic cancer cells Panc-1, and its mechanism.@*METHODS@#On the established human pancreatic cancer cells Panc-1-XS, the expression of XIAP and survivin was inhibited simultaneously. Cell invasion and migration were detected by Transwell chamber experiments and scratch test, and the expression of epithelial marker E-cadherin, mesenchymal markers Slug, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and P-Akt protein was determined by Western blot.@*RESULTS@#Cell invasion and migration of Panc-1-XS cells decreased significantly, accompanied by significantly upregulated protein expression of E-cadherin, and significantly declined protein expression of the Slug, indicating increased mesenchymal-epithelial conversion (MET); and increased protein expression of PTEN, and declined protein expression of P-Akt.@*CONCLUSION@#Simultaneously inhibiting the expression of XIAP and survivin can partially reverse EMT phenotype of pancreatic cancer Panc-1 cells, which then significantly reduces the cell invasion and migration of Panc-1 cell lines. This process may be regulated by PTEN/PI3K/Akt signaling pathway.
Subject(s)
Humans , Antigens, CD , Cadherins , Metabolism , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition , Genetics , Inhibitor of Apoptosis Proteins , Genetics , Metabolism , Neoplasm Invasiveness , PTEN Phosphohydrolase , Metabolism , Pancreatic Neoplasms , Pathology , Proto-Oncogene Proteins c-akt , Metabolism , Signal Transduction , Snail Family Transcription Factors , Survivin , Transcription Factors , Metabolism , X-Linked Inhibitor of Apoptosis Protein , Genetics , MetabolismABSTRACT
0.05).However,the percentage of patients with cholecystolithiassis was 86.5% in IGC group,and 50.6% in GC group(P=0.000).Besides the percentage of IA stage in IGC group(29.7%) was relatively higher than that(9.0%)in GC group(P=0.03);the surgical resection rate of tumor in IGC group was 56.8% and 32.6% in GC group(P=0.01).Nevertheless,the percentage of advance stage in IGC group(43.2%) was relatively lower than that in GC group(74.2%)(P=0.001).The overall 1,3,and 5-year survival rate of IGC group was 70.0%,31.2% and 26.8% repectively,and the mean survival time was17 months(51?13);which were significantly higher than those in GC group,in which the 1,3,5-year survival rate was 27.0%,17.7% and 15.1% repectively and the mean survival time was(25?8),5 months(all P=0.006).Single factor analysis showed that the survival time in IGC patients was influenced by the TNM stage(P=0.000),pT-category(P=0.000),operation-category(P=0.008);however,postoperative pathological grade(P=0.080),age(P=0.188) and sex(P=0.234) had no influence on survival rate.According to multivariate analysis,pT-category(P=0.000)was an independent factor for the survival time of IGC.Conclusions Comparing with GC group,IGC has a higher percentage of cholecystolithiassis,IA tumor stage and surgical resection rate,and thus,it has relatively better progonosis.pT-category is the vital independent prognostic factor in IGC.If a patient in ICG has been misdiagnosed during the primary operation,the patient should be re-operated for radical excision as soon as possible,except when the tumor is in stage Tis or T1a.
ABSTRACT
Objective To investigate the possibility of survivin inhibition by lentiviral vector-mediated RNA interference and the influence on cell apoptosis in pancreatic cancer cell line.Methods The lentiviral vector of SiRNA targeted against survivin(LV-shRNA-survivin-1,LV-shRNA-survivin-2,LV-shRNA-survivin-3) was constructed and transfected into the packaging cells 293T,and then the supernatant with virus was collected to transfect SW1990 cells.Quantitative real-time fluorescent PCR and Western-blot were used to detect the expression of survivin.DAPI staining and detection of enzymatic activity of caspase 3/7 were employed to examine cell apoptosis.Results Three lentiviral vector-survivin-shRNA were constructed successfully.In the LV-shRNA-survivin-1 group,the survivin mRNA and protein expression inhibitory rate was 73.50% and 87.64% respectively;when compared to control group,the activity of caspase-3/7 increased significantly,which showed a 14.5-fold increase,and apoptosis increased 11.95%.Conclusions Lentiviral vector-mediad RNA interference targeted against survivin can effectively inhibit survivin expression and increase cell apoptosis significantly.