ABSTRACT
The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients' outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol-miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.
ABSTRACT
Objective To investigate the effects of cyclooxygenase-2 inhibitor celecoxib on proliferation , invasion and migration of human pancreatic cancer cell line PANC-1 and then determine the optimal concentration of cele-coxib and the most suitable application time .Methods Human pancreatic cancer cell line PANC-1 was treated with diverse concentrations of celecoxib (20,60,100 μmol/L) for different durations (24,48,72 h).Cell prolifer-ation, invasion and migration capabilities were measured by MTT colorimetry , Transwell invasion assay , and scratch assay respectively .Results The proliferation capability of PANC-1 cell was reduced by celecoxib in a con-centration-and time-dependent manner ( P <0.05 ) .In addition , the invasion and migration capabilities were decreased by celecoxib in a concentration-dependent manner(P<0.01).Conclusions Celecoxib attenuates the proliferation of human pancreatic cancer cell line PANC-1 in a concentration-and time-dependent manner .Cele-coxib attenuates the invasion and migration in a concentration-dependent manner .
ABSTRACT
Objective To explore the expression of matrix metalloproteinase-14(MMP-14)protein in the human stomach carcinoma tissues and its correlation with carcinoma invasiveness and metastasis.Methods The MMP-14 protein expression was detected by immunohistochemistry in 59 cases of stomach carcinoma tissues (observation group)and 20 cases of normal stomach tissues (control group,the adjacent normal tissues from the tumor margin of 5 cm confirmed by pathology),and its correlation with the clinically pathological parameters was analyzed.The expression characteristics of MMP-14 among various TNM stages of stom-ach carcinoma were also analyzed.Results The positive rate of MMP-14 expression was 50.85%(30/59)in the observation group and 5.00% (1/20)in the control group,the positive rate of the observation group was significantly higher than that of the control group (P <0.01);the expression level of MMP-14 was correlated with the differentiation degree,regional lymph node metastasis degree,invasion depth,lymphatic invasion and TNM stage,which showing the statistical difference(P < 0.01);the expression of MMP-14 protein was up-regulated and showed the transferring trend from cytoplasm to cellular membrane along with the progres-sion of TNM stage.Conclusion The overexpression of MMP-14 protein exists in stomach carcinoma tissues,which contributing to the invasion and metastasis of stomach carcinoma cells.
ABSTRACT
Objective To investigate the anti-tumor effect and mechanism of curcumin in pancreatic cancer (PC). Methods Smad4 and Jab1 expressions were detected by immunohistochemistry in tumor tissues and pericarcinomatous tis?sue from 35 PC cases, and the correlation of Smad4 and Jab1 were analyzed based on the percentage of positive staining in?tissues from 21 random selected PC cases. The effect of curcumin on expressions of tumor suppressors p53, Smad4 and cell cycle inhibitor p27 were examined by Western Blotting after human pancreatic cancer cell line PANC-1 were divided into PANC-1 control group (no treatments were given) and PANC-1 curcumin group (treated with cell culture medium containing 10μmol/L curcumin). The effect of curcumin on expressions of combination of β-TrCP1 and Smad4 was examined by Co-Immunoprecipitation after human embryonic kidney cell line 293T were divided into 293T control group (no treatments were given), 293T curcumin group (treated with cell culture medium containing 10μmol/L curcumin) and 293T Jab1 group (trans?fected by HA-Jab1 plasmid). Results Compared with expressions in pericarcinomatous tissues, Smad4 was down regulated while the expression of Jab1 was upregulated in PC tissues (P<0.01), and the expression of Smad4 was negatively correlated with the expression of Jab1 (n=21, r=-0.71, P=0.007). After treated with curcumin, the protein expression of p53, Smad4 and p27 was increased in PANC1 cell, and the protein expression of the combination ofβ-TrCP1 and Smad4 was decreased in 293T cell (P<0.05). After transfected by HA-Jab1 plasmid, the protein expression of the combination ofβ-TrCP1 and Smad4 was increased in 293T cell (P<0.05). Conclusion Curcumin may have suppression effect of PC through increasing the protein expression of p53, Smad4 and p27, and the mechanism of Smad4 upregulation may be related with the inhibition of Smad4 ubiquitination process, while Jab1 may be also involved in Smad4 degradation through ubiquitination.
ABSTRACT
Objective To study the effect of fat emulsion intravenous infusion on serum free fatty acids(FFAs) in rats.Methods 24 male Wistar rats were divided randomly into 3 groups,8 rats in each group.(1)Control group(NS),the rats were infused with normal saline intravenously and regular chow;(2)Group LCT,infused with 10% intralipid fat emulsion intravenously;(3)Group MCT/LCT,infused with 10% lipofundin fat emulsion. Group LCT and group MCT/LCT were continuously received equal calorie,nitrogen and volemin in 'All-in-One'solutions. Serum samples were drawn on the 8th day after PN for fatty acid determination. Results The FFAs in Group LCT and group MCT/LCT were remarkably higher than that in control group, but no difference between Group LCT and group MCT/LCT. Conclusions Fat emulsion intravenous infusion can increase the serum free fatty acids considerately.