| Objective To evaluate the expression of macrophage migration inhibitor factor (MIF) and cyclinD1 in pancreatic carcinoma and their relationship with clinical pathology characteristics.Methods The expression of MIF and CyclinD1 in 4 pairs pancreatic tumor tissues (T) and their peri-tumor tissues (P) was initially detected to provide evidence of simultaneous MIF and CyclinD1 overexpression in pancreatic tumor tissues . Specific small interfering RNA targeting MIF gene was chemically synthesized, and then was transfected at the doses of 50nmol/L and 100nmol/L into pancreatic tumour cell lines of PANC-1 and Bxpc-3 with lipofectamine 2000 methods. The control groups of PANC-1 and Bxpc-3 were transfected with the control siRNA. The expression of MIF,CyclinD1 mRNA and MIF,CyclinD1 protein were examined by PCR and western blot after siRNAs treatment, respectively. The results were compared with the control groups and the experimental group.The expressions of MIF and cyclinD1 in 89 carcinoma and 5 normal pancreatic tissues were detected with immunohistochemistry methods, and the relationships among MIF and cyclinD1 expression and clinicopathological factors was studied. Results MIF and CyclinD1 were overexpressed in the pancreatic carcinoma tissues compared with the peri-tumor tissues or normal pancreatic tissues(P<0.01). In MIF siRNA treated PANC-1 and Bxpc-3 cells, the mRNA and protein expression of MIF were significantly decreased in a dose-dependent manner. CyclinD1 mRNA was observed to be significantly down-regulated in MIF siRNA treated PANC-1 and Bxpc-3 cells when compared with the control groups(P<0.01). In 50nmol/L and 100nmol/L groups, MIF,CyclinD1 mRNA levels were respectively decreased by(54.2±3.7)%å'Œ(32.0±5.0)% and(86.5±3.7)%å'Œ(73.0±3.0)% in PANC-1 cell and (42.0±2.1)%å'Œ(40.6±7.0)% and(88.0±1.0)%å'Œ(63.8±6.0)% in Bxpc-3 cell. To be compared with the control groups, MIF,CyclinD1 protein levels were significantly reduced in the experimental groups(P<0.01)and a statistically significant difference of the protein expression were also found between the two different doses groups of MIF siRNA treated pancreatic tumor cells(P<0.01). The overexpression of MIF had a significant correlation with I, II, III, IV tumor stage (69.2%, 94.7%, 96.4%, 100%, P <0.05),while the positive expression rate of cyclinD1 only had a significant correlation with tumor stages III,IV(33.3%, 68.8%, p<0.05). Both of the two proteins had a correlative tendency with pathological grade and lymph node metastasis. The different expression of MIF between pancreatic carcinoma with and without liver metastasis had no statistical significance, (100%, 85.9%, p>0.05)while there was a statistically significant difference about cyclinD1 (66.7% , 46.5%,p<0.05). A significant positive correlation was also found between MIF and cyclinD1 (p<0.05).Conclusions MIF and CyclinD1 protein and mRNA were overexpression in pancreatic tumor tissues.MIF siRNA was able to specifically knock down the expression of MIF and it could also efficiently suppress the expression of CyclinD1 in PANC-1 and Bxpc-3 cells. The expression of MIF and CyclinD1 was higher in pancreatic cancer tissues than in nperi-tumor tissues or normal pancreatic tissues, and they may be associated to the malignant stage, tumor differentiation, local lymph node and liver metastasis of this deadly tumor. |
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