Objective To investigate the mechanism of the resistance of pancreatic cancer cells to tumor necrosis factor related apoptosis inducing ligand (TRAIL)mediated apoptosis. MethodsThe expression of TRAIL receptor-4 (TRAIL-R4) in normal pancreas tissue and pancreatic cancer was analyzed by using Northern blotting, Western blotting and immunohistochemistry.ResultsTRAIL-R4 mRNA and protein were expressed at moderate to high levels in human pancreatic cancer, but demonstrated weak to negative in the normal pancreas. Moreover, pancreatic cancer cells showed b TRAIL-R4 immunostaining throughout the tumor mass. Conclusion TRAIL-R4 levels are significantly different in pancreatic cancer in comparison to the normal pancreas. These findings give new insights into the resistance mechanisms of pancreatic cancer cells towards TRAILmediated apoptosis.
ObjectiveTo study the effects of angiogenesis inhibitor SU5416 on the microvessel density(MVD) of pancreatic cancer and to evaluate its influence on the growth and metastasis of pancreatic cancer. Methods A rat model of pancreatic cancer was established with dimethylbenzanthracine(DMBA). 60 rats with pancreatic cancer were randomly divided into 4 groups: saline group, 5-Fu group, SU5416 group, 5-Fu and SU5416 group. Thirteen weeks after injection, the microvascular density (MVD) of pancreatic cancer was detected.Results The microvascular densities (MVD) were (12.3±3.2)%, (11.4±3.8)%, (2.1±1.5)% and (1.8±1.1)% in the saline group, 5-Fu group, SU5416 group and 5-Fu+SU5416 group respectively. The MVDs in the SU5416 group and 5Fu+SU5416 group were statistically lower than those in the saline group and 5-Fu group(P＜0.05). There was no significant difference between the 5-Fu group and saline group(Pgt;0.05). ConclusionSU5416 can inhibit the microvascular growth in pancreatic cancer. And the inhibition can be enhanced when combined with chemotheraputic drugs.
Objective To investigate the invasion ability of Panc-1 cells in vivo and in vitro af ter being t ransfected with tissue factor pathway inhibitor 2 gene ( TFPI-2) . Methods The expression vector pEGFP-C1-TFPI-2 was transfected into human pancreatic cancer line Panc-1 cells by using liposome. TFPI-2 mRNA and protein of transfected and nontransfected cells were detected by reverse t ranscription-polymerase chain reaction (RT-PCR) and Western blot respectively. The tumor cells invasive behavior of t ransfected ( Panc-1-TFPI-2) and nontransfected ( Panc-1-V and Panc-1-P) cells were assessed in vitro through Boyden Chamber method. The transfected and nontransfected cells were implanted into nude mice to observe it s growth and metastasis in vivo. Results Expressions of mRNA and protein of TFPI-2 were confirmed in transfected cells. Af ter TFPI-2 t ransfection , the number of Panc-1-TFPI-2 , Panc-1-V and Panc-1-P cells passing through membrane of Boyden Chamber were 24. 4 ±3. 5 ,61. 3 ±4. 1 and 60. 2 ±3. 9 , respectively. The number of TFPI-2-expressing cells to t raverse a Matrigel-coated membrane was obviously decreased compared with that of non-expressing cells , the invasion ability was lower than that before transfection in vitro. The subcutaneous tumor volume of the Panc-1-TFPI-2 group was (438. 0 ±69. 8) mm3 , the Panc-1-V group was (852. 0 ±102. 9) mm3 and the Panc-1-P group was (831. 0 ±78. 1) mm3 , P lt; 0. 05. The metastasis to liver and lung and muscular invasion occurred in the Panc-1-V group and the Panc-1-P group. There were no muscular invasion and metastatic lesions in the Panc-1-TFPI-2 group. Conclusion TFPI-2 gene expression may obviously inhibit the invasion ability of pancreatic cancer cells in vitro and in vivo , which provides an experimental basis for the treatment of human pancreatic cancer by gene therapy.
Objective To detect the activity of lactate dehydrogenase (LDH) and LDH isoenzyme, and to explore the relation between biological behavior ofpancreatic cancer and glycolysis. MethodsConsecutive 12 cases of pancreatic ductal adenocarcinoma and 12 benign lesions such as insulinoma from October 2006 to July 2008 were collected, as well as normal pancreatic tissues. The total activity of the LDH was detected by the LDH testing kits, and the iosenzyme pattern of LDH was inspected by the France Sebia hydrasys. ResultsCompared to the normal tissue, LDH activity ofpancreatic cancer and adjacent non-cancerous tissue was significantly higher (P＜0.05). LDH iosenzyme pattern in cancer tissue was also significantly different, the percentage of LDH4 and LDH5 increased obviously, and were greater than that innormal tissue (P＜0.05). ConclusionThe alteration of LDH activity and its isoenzyme pattern are possibly related to the pathogenesis of pancreatic cancer. Inhibit the LDH activity may be a new therapeutic strategy.
Objective To observe the expression of Galectin-3 and Galectin-1 in pancreatic cancer and explore the relationship between the expression and pathological grading. Methods Forty specimens of pancreatic carcinoma tissue and thirty-one specimens of normal pancreas tissue were selected, which were confirmed by surgical resection and pathology from 2002 to 2009. The expression of Galectin-3 mRNA and Galectin-1 mRNA in pancreatic cancer cell lines SW1990, PANC-1 and ASPC -1 was detected by means of reverse transcriptase-polymerase chain reaction; the expression of Galectin-3 protein and Galectin-1 protein in SW1990, PANC-1 and ASPC-1 was detected by means of immunocytochemistry; the expression of Galectin-3 protein and Galectin-1 protein in pancreatic cancer and normal pancreatic tissue was detected by means of immunohistochemistry. Results In SW1990, PANC-1 and ASPC-1, Galectin-3 mRNA signal and protein were detected, but no Galectin-1 mRNA signal or protein was detected. There was no expression of Galectin-3 protein or Galectin-1 protein in the 31 specimens of normal pancrease tissue, while there were Galectin-3 protein and Galectin-1 protein expressed in the 40 specimens of pancreatic cancer tissue. In the 40 specimens of pancreatic cancer tissue, the expression of Galectin-3 protein was observed in pancreatic cancer cells, but not in fibroblasts or matrix cells around the cancer mass; while the expression of Galectin-1 protein was observed in fibroblasts and matrix cells around the cancer mass, but not observed in pancreatic cancer cells. There was no significant association between the expression of Galectin-3 protein in pancreatic cancer and pathological grading (P>0.05); while the expression of Galectin-1 protein in pancreatic cancer was related to the pathological grading, and the expression of Galectin-1 protein was significant higher in poorly differentiated tumors than that in well/moderately differentiated tumors (P<0.05). Conclusions Galectin-3 or Galectin-1 is not expressed in normal pancreases; Galectin-3 is expressed in pancreatic cancer cells; Galectin-1 is expressed in fibroblasts and matrix cells around the cancer mass. The expression of Galectin-1 is related with the differentiation of pancreatic cancer.
ObjectiveTo review the research advances about myeloid derived suppressor cells(MDSC)and pancreatic cancer, and explore the future research trends. MethodRelated literatures in recent 5 years from abroad databases(PubMed, Web of Science, and EMBASE)and domestic databases(CNKI, WANFANG, and WEIPU)were collected and reviewed. ResultsThe MDSC was the core of tumor immune regulation network in pancreatic cancer microenvironment, it formed a complicated feedback with the pancreatic cancer and the stellate cells. MDSC could promote the cancerogensis and progression of pancreatic cancer, and the accumulation of MDSC in peripheral blood of pancreatic cancer patient could predict the poor prognosis. However up to now, the literatures about the relation between MDSC and the chemotherapy and metastasis of pancreatic cancer were limited. ConclusionsThe comprehensive therapy by targeting MDSC of pancreatic cancer is promising. However, many issues need to be further investigated.
Objective To observe the effect of epidermal growth factor (EGF) on the proliferation, adhesion, invasiveness and the activation of nuclear factor-κB (NF-κB), matrix metalloproteinases (MMPs) expression and explore related mechanisms in pancreatic cancer cells. Methods Cell invasion assay, proliferation assay and adhesion assay were used to examine the proliferation, adhesion and invasiveness of pancreatic cancer cells, respectively. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA), and MMPs protein and mRNA expressions were investigated by gelatin zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Results EGF increased the invasiveness of pancreatic cancer cell in a dose-dependent manner (P＜0.05), but did not affect cell proliferation or adhesion. The expressions of MMP-9 mRNA and protein significantly increased after induction by EGF and were highest when EGF concentration was 50 ng/ml, while there was no effect on the expressions of MMP-2 mRNA and protein. Furthermore, NF-κB activity increased with increased concentration of EGF in a concentration-dependent manner (P＜0.05). In addition, NF-κB activity and the expressions of MMP-9 mRNA and protein by pretreatment with both pyrrolidine dithiocarbamate (PDTC) and EGF decreased when compared that by pretreatment with EGF alone. The invasiveness of pancreatic cancer cell by pretreatment with both PDTC and EGF decreased when compared that by pretreatment with EGF alone and nothing (P＜0.05).Conclusion The findings indicate that the NF-κB-mediated MMP-9 induction is essential for EGF-induced invasiveness in pancreatic cancer cells, which can be inhibited by PDTC.
Objective To introduce the research progress in the effect of chemotherapeutic resistance of metabolic enzymes of gemcitabine to pancreatic cancer.Methods Recent literatures about metabolic enzymes that played key roles in mediating gemcitabine chemotherapeutic resistance of pancreatic cancer were collected and reviewed. Results The metabolic enzymes of gemcitabine, such as hENT1, dCK, RRM1 and CDA, were closely related to chemotherapeutic resistance of pancreatic cancer. The relationship between the single nucleotide polymorphism of metabolic enzymes and the resistance to gemcitabine remained to be clarified. Conclusion Multiple factors are involved in the mechanism of chemotherapeutic resistance of pancreatic cancer to gemcitabine, which needs further research.
ObjectiveTo investigate the expression of ubiquitin-specific protease 9X (USP9X) in pancreatic cancer, and to evaluate the correlation of USP9X with the survival of patients with pancreatic cancer. MethodThe expression of USP9X was detected in 55 pieces of surgically resected primary pancreatic cancer tissues and adjacent nontumorous pancreatic tissues by streptavidin-perosidase immunohistochemical method. ResultsThe rate of USP9X high expression in the 55 pieces of the primary pancreatic cancer tissues was 58.2% (32/55), which in the adjacent nontumorous pancreatic tissues was zero. The expression of USP9X was not correlated with the gender, age, tumor position, or tumor size (P > 0.05), while which was significantly correlated with the differentiation degree, lymph node metastasis, or TNM stage (P < 0.05). By using Cox proportional hazard model, the multivariable analysis revealed that the differentiation degree, lymph node metastasis, and USP9X expression were the independent risk factors. Survival of the patient with USP9X high expression was significantly shorter than that with USP9X low expression (P < 0.05), and there was the same result in the patients with stageⅡ, with lymph node negative, or intermediate differentiation degree (P < 0.05). ConclusionThe results indicate that USP9X might play an important role in the pathogenesis and prognosis of pancreatic cancer.
Objective To search for the significant gene indicators in the diagnosis of pancreatic cancer. Methods Literatures about genetic diagnosis of pancreatic cancer were collected and reviewed. Results K-ras, p53, DPC4 and telomerase genes were considered to play important roles in the diagnosis of pancreatic cancer. Conclusion Detection of the genes related to pancreatic cancer may be of helpful in early diagnosis of pancreatic cancer.