ObjectiveTo explore the mechanisms of perineural invasion (PNI) in pancreatic cancer so as to find a new treatment for pancreatic cancer. MethodsThe literatures on PNI, neurotropism, nerve-tumor microenvironment and nerve growth factor in pancreatic cancer were reviewed and the mechanisms of PNI were summarized. ResultsThe rich innervation of pancreatic tissue itself and the minute slits within perineural structure were the anatomic basis of PNI. Tumor cells expressed neural antigens were the pathological basis of PNI. Tumor-nerve microenvironment and nerve growth factor family and themselves receptors might play an important molecular role in PNI. However, tumor cells expressed neural antigens were not only closely related to the PNI, but also the interaction between tumor cells and nerves played an important role in PNI. ConclusionsThe detailed mechanisms of PNI are extremely complex and controversial up to today. However, it is possible to search a new therapeutic target in pancreatic cancer according to the mechanisms of PNI.
ObjectiveTo investigate the growth characteristics of pancreatic cancer cells in the twodimensional culture system (monolayer) and threedimensional culture system (type Ⅰ collagen and extracellular matrix gel). MethodsThree pancreatic cancer cell lines (SW1990, PCT, and ASPC1) were cultured in monolayer, type Ⅰ collagen, and extracellular matrix gel, respectively. The growth patterns were observed, growth curves were detected by CCK8 test, and the cell cycle distributions were analyzed by propidium iodide staining. Results In the twodimensional culture system, cells grew in monolayer. In the type Ⅰ collagen and the ECM gel threedimensional culture system, cells formed multicellular spheroids (MCS), of which the growth rates were slower than those of the cells in monolayer. The proportions of S phase of SW1990, PCT, and ASPC1 cells in twodimensional culture system were significantly more than those in the type Ⅰ collagen on 4 d and 8 d 〔(29.6±3.0)% vs. (18.2±5.1)%, (33.6±2.1)% vs. (14.5±3.2)%, (33.1±1.8)% vs. (24.7±2.6)%; Plt;0.05〕, while the difference of proportion of three cell lines in G2/M phase was not different between twodimensional culture system and type Ⅰ collagen (Pgt;0.05). The proportions of G0/G1 phase of SW1990 and PCT cells cultured in the type Ⅰ collagen on 4 d and 8 d and ASPC1 cells cultured in the type Ⅰ collagen on 4 d were significant more than those cultured in twodimensional culture system (Plt;0.05). The proportions of S phase of ASPC1 cells and SW1990 cells cultured in the type Ⅰ collagen on 4 d were significant more than those cultured in the type Ⅰ collagen on 8 d (Plt;0.05). ConclusionsThe characteristics of pancreatic cancer cells in twodimensional and threedimensional culture systems are different. MCS culture system can better mimic the in vivo growth environment of cells in tumors.
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.
【Abstract】Objective To analyze the function of BAG3 in antiapoptosis and chemotherapy resistance induction process of pancreatic cancer.Methods The expressions of BAG-3 in pancreatic cancerous tissues of patients with chemotherapy and those without chemotherapy before resection were determined by immunohistochemistry. The expression difference of BAG-3 protein 18 hours after cultured with chemotherapy drugs (concentration of drugs: 5-FU 50 μg/ml, MMC 0.5 μg/ml, EADM 1.5 μg/ml) of 3 pancreatic cancer cell lines （MIACaPa-2, PANC-1, SW1990） was measured through Western blotting method.Results The median positive rate of pancreatic cancer tissue from patients accepted chemotherapy before resection was higher than those not accepted chemotherapy, but there wasn’t significant difference. Eighteen hours after cultured with drugs, the level of BAG-3 of this three cell lines had significant increased compared with control group (P＜0.05). Conclusion Chemotherapy induces elevation of BAG-3 expression of pancreatic cancer. The upregulate of BAG-3 may associate with the chemotherapy resistance induced by drugs.
【Abstract】ObjectiveTo establish adriamycin (ADM) resistant pancreatic cancer cell line SW1990/ADM and to investigate its drug resistance mechanism.MethodsADM-resistant pancreatic cancer cell line SW1990/ADM was obtained by culture of pancreatic cancer cell line SW1990 in vitro with intermittently increasing the concentration of ADM in the culture medium for ten months. After two months of drug free culture, its biological characteristics, drug sensitivity as well as the expression and function of multidrug resistant gene 1 (mdr1) were detected, respectively. ResultsCompared with the parental cell line, SW1990/ADM showed great changes in biological characteristics and developed a cross resistance to various chemotherapy drugs. The drug resistance indexes of cell line SW1990/ADM to ADM, mitomycin, fluorouracil and gemcitabine were 49.60, 7.25, 3.80 and 1.25, respectively. The level of mdr1 mRNA expression in cell line SW1990/ADM was much higher than that of the parental cell line（P＜0.01). ConclusionWe have established adriamycin resistant pancreatic cancer cell line SW1990/ADM with multidrug resistance phenotype, its multidrug resistance is positively relevant to the expression of mdr1.
【Abstract】Objective To investigate the relationship between the development of pancreatic cancer and inflammation, and the therapy strategy.Methods Related articles were reviewed.Results The pathogenesis of inflammation in pancreatic cancer development involves cytokines, NF-κB, COX-2, PPAR-γ, DNA damage, gene changes，etc. Based on these mechanisms some medications are under developing. Conclusion Accumulative effects of pancreatic inflammation may lead to DNA changes, and even pancreatic cancer development. Medications aimed at suppressing pancreatic inflammation may help with prevention and treatment of pancreatic cancer.
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 study the basic and clinical achievements in diagnosis and therapy of hereditary pancreatitis. Methods Related literatures of recent years were reviewed. Results Hereditary pancreatitis was a rare type of pancreatitis, with an estimated penetrance of 80%, and was believed to be caused by a mutation in the cationic trypsinogen gene. Patients with hereditary pancreatitis had a high frequency of pancreatic cancer.Conclusion The progress has been made on hereditary pancreatitis and has given us many useful suggestions for a better understanding about this difficult medical problem.
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.
bjectiveTo study the therapeutic effect and mechanism of photodynamic therapy (PDT) to the nude mice model of pancreatic cancer by intratumoral injecting photosensitizers hematoporphyrin derivatives (HpD), hypocrellin A (HA) and 2butylamino2demethoxyhypocrellin A (2BA2DMHA).MethodsThe animal model of human pancreatic cancer was developed by injecting human pancreatic cancer cells SW1990 into the back of the nude mice. After photosensitizers HpD, HA and 2BA2DMHA was given by the intratumoral injection, the 632.8 nm HeNe laser was used to irradiate the tumor. The curative effect was recorded and factorⅧ was used in the immunohistochemical staining to study the vessel change. ResultsPDT can destroy the pancreatic neoplasm, the tumor growth rate was significantly reduced after PDT. The immunohistochemical staining showed PDT could make injury to vessel endothelial cell.ConclusionPDT can induce injuries of pancreatic cancer; vascular injury is an important way to exert function.