• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2503-2509
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• 2012

Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.167-174
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• 2014

Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore investigated the effects of barbigerone on all three in the B16F10 tumor model established in both zebrafish and mouse models, and explored underlying molecular mechanisms. In vitro, barbigerone inhibited B16F10 cell proliferation, survival, migration and invasion and suppressed human umbilical vascular endothelial cell migration, invasion and tube formation in concentration-dependent manners. In the transgenic zebrafish model, treatment with $10{\mu}M$ barbigerone remarkably inhibited angiogenesis and tumor-associated angiogenesis by reducing blood vessel development more than 90%. In vivo, barbigerone significantly suppressed angiogenesis as measured by H and E staining of matrigel plugs and CD31 staining of B16F10 melanoma tumors in C57BL/6 mice. Furthermore, it exhibited highly potent activity at inhibiting tumor growth and metastasis to the lung of B16F10 melanoma cells injected into C57BL/6 mice. Western blotting revealed that barbigerone inhibited phosphorylation of AKT, FAK and MAPK family members, including ERK, JNK, and p38 MAPKs, in B16F10 cells mainly through the MEK3/6/p38 MAPK signaling pathway. These findings suggested for the first time that barbigerone could inhibit tumor-angiogenesis, tumor growth and lung metastasis via downregulation of the MEK3/6/p38 MAPK signaling pathway. The findings support further investigation of barbigerone as a potential anti-cancer drug.

• Biomedical Science Letters
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• v.25 no.1
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• pp.107-112
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• 2019

The corpus luteum (CL) is composed to various cells, such as luteal steroidogenic cells (LSCs), luteal thecal steroidogenic cells (LTCs), luteal endothelial cells (LECs), fibroblast, immune cells and blood cells. The life span of CL is controlled by proliferation and apoptosis of luteal cells. Therefore, this study investigated apoptotic factors in luteal cells derived from bovine CL. The CL tissues were collected from bovine ovaries and luteal cells were isolated from middle phase CL. Then, LTCs and LECs were separated according to cellular morphology from LSCs. The expression of Bax, Bcl-2, Fas and tumor necrosis factor 1 receptor (TNF1R) mRNA and protein were analyzed using quantitative RT-PCR and western blot. Results show that, Bax and TNFR1 mRNA expression were significantly increased at late group than early and middle groups, otherwise Bcl-2 were significantly decreased at late group than early group (P<0.05). Fas mRNA expression were significantly decreased in middle group compared to early and late groups (P<0.05). In addition, Bax and Bcl-2 mRNA in LTCs was lower than LSCs, Fas mRNA was higher than LSCs. The Bcl-2 protein expression was lower at LTCs than LSCs, especially Fas protein in LTCs was significantly lower than LSCs and LECs (P<0.05). Otherwise, TNFR1 protein of LTCs were similar with LSCs but higher compared with LECs. In conclusion, we suggest that the results may help understanding of apoptosis ability in luteal cells according to cell type during CL regression of estrous cycle.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.5
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• pp.479-491
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• 2024

Improving liver regeneration (LR) remains a medical issue, and there is currently a lack of safe and effective drugs for LR. Rhizoma Dioscoreae (SanYak, SY) is a traditional Chinese medicine. However, the underlying action mechanism of SY treatment for LR is yet to be fully elucidated. To explore the mechanism by which SY affects LR, we have conducted a series of methods for network pharmacological analysis, molecular docking, and in vivo experimental validation in mice. Overall, 9 compounds and 30 predicted target genes of SY were found to be associated with the therapeutic effects of LR. Compared with the model group, hematoxylin and eosin staining revealed that the mice with preoperative drug intervention possessed fewer postoperative hepatocyte bubbles and relatively regular morphology. Furthermore, the serum alanine transaminase and aspartate aminotransferase levels were reduced, immunohistochemistry revealed elevated proliferating cell nuclear antigen positivity rate, and Western blotting demonstrated that the phospho-protein kinase B (AKT)/AKT ratio was downregulated and that vascular endothelial growth factor A (VEGFA) expression levels were upregulated. This study explored dioscin, the main active ingredient of SY, and its potential therapeutic effects on LR. It repairs damaged liver following surgery and promotes liver cell proliferation. The action mechanism comprises reducing AKT phosphorylation levels and upregulating VEGFA expression levels. Thus, this study provides a new direction for further research on the mechanism of SY promoting LR.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9319-9325
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• 2014

Alkaloids are the most extensively featured compounds of natural anti-tumor herbs, which have attracted much attention in pharmaceutical research. In our previous studies, a mixture of major three alkaloid components (5, 6-dihydrobicolorine, 7-deoxy-trans-dihydronarciclasine, littoraline) from Hymenocallis littoralis were extracted, analyzed and designated as AHL. In this paper, AHL extracts were added to human liver hepatocellular cells HepG-2, human gastric cancer cell SGC-7901, human breast adenocarcinoma cell MCF-7 and human umbilical vein endothelial cell EVC-304, to screen one or more AHL-sensitive tumor cell. Among these cells, HepG-2 was the most sensitive to AHL treatment, a very low dose ($0.8{\mu}g/ml$) significantly inhibiting proliferation. The non-tumor cell EVC-304, however, was not apparently affected. Effect of AHL on HepG-2 cells was then explored. We found that the AHL could cause HepG-2 cycle arrest at G2/M checkpoint, induce apoptosis, and interrupt polymerization of microtubules. In addition, expression of two cell cycle-regulated proteins, CyclinB1 and CDK1, was up-regulated upon AHL treatment. Up-regulation of the Fas, Fas ligand, Caspase-8 and Caspase-3 was observed as well, which might imply roles for the Fas/FsaL signaling pathway in the AHL-induced apoptosis of HepG-2 cells.

• Tuberculosis and Respiratory Diseases
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• v.62 no.1
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• pp.43-50
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• 2007

Background: Mutated or deregulated expression of C-erbB-2 causes this gene to function as a potent oncogene. Vascular endothelial growth factor (VEGF) is a crucial angiogenic molecule in lung cancer. Both C-erbB-2 and VEGF can promote growth, proliferation and metastasis in non-small cell lung cancer (NSCLC). The purpose of this study was to investigate evaluate the relationship between the expressions of the C-erbB-2 and VEGF genes using immunohistochemistry. Materials and Methods: Ninety-five patients with NSCLC were involved (60 squamous cell carcinoma and 35 adenocarcinoma). The formalin-fixed paraffin embedded specimens were immunohistochemically stained for C-erbB-2 and VEGF using the avidin-biotin complex method. Results: Positive C-erbB-2 expression was observed more often in adenocarcinomas than squamous cell carcinomas (p<0.05). Although the immunohistochemical expressions of C-erbB-2 and VEGF in non-small-cell lung cancer showed increased tendencies at an advanced stage, the correlation between early and advanced cancers was insignificant. In adenocarcinomas, the expressions of VEGF and C-erbB-2 were significantly (p<0.05). Conclusion: The overexpression fo C-erbB-2 was significantly higher in adenocarcinomas than squamous cell carcinomas, and correlated with the expression of VEGF in adenocarcinomas of the lungs.

• Macromolecular Research
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• v.9 no.2
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• pp.107-115
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• 2001

Poly(L-lactide-co-glycolide)(PLGA) was blended with poly[$\omega$-methacryloyloxyethyl phospho-rylcholine-co-ethylhexylmethacrylate (PMEH)] (PLGA/PMEH) to endow with new functionality i.e., to improve the cell-, tissue- and blood-compatibility. The characteristics of surface properties were investigated by measurement of contact angle goniometer, Fourier-transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) and electron spectroscopy for chemical analysis (ESCA). NIH/3T3 fibroblast and bovine aortic endothelial cell were cultured on control and PLGA/PMEH surfaces for the evaluation of ceil attachment and proliferation in terms of surface functionality such as the concentration of phosphoryl-choline. Also, the behavior of platelet adhesion on PLGA/PMEH was observed in terms of the surface functionality. The contact angles on control and PLGA/PMEH surfaces decreased with increasing PMEH content from 75$^{\circ}$ to about 43$^{\circ}$. It was observed from the FTIR-ATR spectra that phosphorylcholine groups are gradually increased with increasing blended amount of MPC. The experimental P percent values from ESCA analysis were more 3.28∼7.4 times than that of the theoretical P percent for each blend films. These results clearly indicated that the MPC units were concentrated on the surface of PLGA/PMEH blend. The control and PLGA/PMEH films with 0.5 to 10.0 wt% concentration of PMEH were used to evaluate cell adhesion and growth in terms of phosphorylcholine functionality and wettability. Cell adhesion and growth on PLGA/PMEH surfaces were less active than those of control and both cell number decreased with increasing PMEH contents without the effect of surface wettability. It can be explained that the fibronectin adsorption decreased with an increase in the surface density of phosphorylcholine functional group. One can conclude the amount of the protein adsorption and the adhesion number of cells can be controlled and nonspecifically reduced by the introduction with phosphorylcholine group. Morphology of the adhered platelets on the PLGA/PMEH surface showed lower activating than control and the number of adhered platelets on the PLGA/PMEH sample decreased with increasing the phosphorylcholine contents. The amount of fibrinogen adsorbed on the PLGA/PMEH surface demonstrated that the phospholipid polar group played an important role in reducing protein adsorption on the surface. In conclusion, this surface modification technique might be effectively used PLGA film and scaffolds for controlling the adhesion and growth of cell and tissue, furthermore, blood compatibility of the PLGA was improved by blending of the MPC polymer for the application of tissue engineering fields.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.6
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• pp.671-680
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• 2017

This study was conducted to examine the effects and potential mechanisms of action of black soybean extracts and fermented black soybean extracts by Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animals subsp. lactis BB-12 (BB-12) on proliferation of human follicle dermal papilla cells (HFDPC). We examined changes in pH, total polyphenol, sugar, and reducing sugar contents according to fermentation period of black soybean extracts. Assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was performed to determine cell toxicity levels of the four black soybean extracts [black soybean water extract (BWE), black soybean ethanol extract (BEE), fermented BWE (F-BEW), and fermented BEE (F-BEE)]. Changes in mRNA expression levels of hair growth promoting factors and hair growth inhibiting factors by the four black soybean extracts were measured by real-time PCR. In addition, phosphorylation levels of mitogen-activated protein kinase family proteins were measured by western blot analysis. As a result, fermentation of black soybeans significantly reduced pH, total polyphenols, and sugar/reducing sugar contents. All four black soybean extracts showed no cellular toxicity in HFDPC. In fact, BEE significantly enhanced cell viability of HFDPC at $100{\mu}g/mL$ compared to control. BWE, BEE, and BWE-F significantly increased mRNA expression of vascular endothelial growth factor, and all four extracts increased mRNA expression of fibroblast growth factor. However, mRNA expression levels of apoptosis-related genes were not affected by black soybean extracts in HFDPC. Furthermore, BWE, BEE, and BWE-F significantly increased phosphorylation levels of extracellular signal-regulated kinase compared to control. Taken together, we demonstrated that black soybean extracts enhanced proliferation of human follicle dermal papilla cells partially via activation of hair growth promoting factors, although no particular significant effects on proliferation were observed by fermentation of black soybeans.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6829-6835
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• 2014

Chemotherapy is the primary therapy for malignant lymphoma (ML). However, the clinical outcome is still far from satisfactory. Consequently, an understanding of the mechanism of modulating cancer cell invasion, migration and metastasis is important for the development of more effective chemotherapeutic agents. FNC, 2'-deoxy-2'-${\beta}$-fluoro-4'-azidocytidine, a novel cytidine analogue, has demonstrated significantly inhibitory effects on proliferation of several non-Hodgkin lymphoma (NHL) cell lines. A previous study indicated that FNC effectively inhibited the growth of Raji and JeKo-1 cells in dose-time dependent effects with $IC_{50}$ values of $0.2{\mu}M$ and $0.097{\mu}M$, respectively. This study was focused on investigating the anti-invasive properties of FNC on NHL cells and its potential mechanisms of action. Cell adhesion and transwell chamber assays were utilized to investigate the anti-invasive effects of FNC on Raji and JeKo-1 cells. Real-time PCR and Western blotting were employed to qualify the expression of ${\beta}$-catenin, the glycogen synthase kinase-3 beta (GSK-$3{\beta}$), E-cadherin vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The results revealed that FNC remarkably inhibited the adhesion, migration and invasion of two human aggressive non-Hodgkin lymphoma cell lines in a dose dependent manner. Furthermore, ${\beta}$-catenin, MMP-2, MMP-9, VEGF mRNA and protein levels were decreased after FNC treatment, while GSK-$3{\beta}$ and E-cadherin increased. Our studies thus provide evidence and a rationale that FNC may offer an effective chemotherapeutic agent by regulating the invasion and metastasis of aggressive non-Hodgkin lymphoma via inhibition of the Wnt/${\beta}$-catenin signaling pathway.

• Journal of Chest Surgery
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• v.39 no.11 s.268
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• pp.828-837
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• 2006

Background: Tissue hypoxia is characteristic of many human malignant neoplasm, and hypoxia inducible factor-1(HIF-1) plays a pivotal role in essential adaptive response to hypoxia, and activates a signal pathway for the expression of the hypoxia-regulated genes, resulting in increasing $O_2$ delivery or facilitating metabolic adaptation to hypoxia. Increased level of HIF-$1{\alpha}$ has been reported in many human malignancies, but in non-small cell lung carcinoma the influence of HIF-$1{\alpha}$ on tumor biology, including neovascularization, is not still defined. In present study the relationship of HIF-$1{\alpha}$ expression on angiogenetic factors, relationship between the tumor proliferation and HIF-$1{\alpha}$ expression, interaction of HIF-$1{\alpha}$ expression and p53, and relationship between HIF-$1{\alpha}$ expression and clinico-pathological prognostic parameters were investigated. Material and Method: Archival tissue blocks recruited in this study were retrieved from fifty-nine patients with primary non-small cell lung carcinoma, who underwent pneumonectomy or lobectomy from 1997 to 1999. HIF-$1{\alpha}$, VEGF(vascular endothelial growth factor), and p53 protein expression and Ki-67 labeling index in tumor tissues were evaluated, using a standard avidin-biotin-peroxidase complex(ABC) immunohistochemistry. Relationship between the HIF-$1{\alpha}$ expression and VEGF, p53 overexpression and correlation between the HIF-$1{\alpha}$ expresseion and Ki-67 index were analyzed. Clinico-pathologic prognostic parameters were also analyzed. Result: HIF-$1{\alpha}$ expression in cancer cells was found in 24 of 59 cases of non-small cell lung carcinoma(40.7%). High HIF-$1{\alpha}$ expression was significantly associated with several pathological parameters, such as pathological TMN stage(p=0.004), pT stage(p=0.020), pN stage (p=0.029), and lymphovascular invasion(p=0.019). High HIF-$1{\alpha}$ expression was also significantly associated with VEGF immunoreactivity(p<0.001), and aberrant p53 expression(p=0.040). but was marginally associated with Ki-67 labeling index(p=0.092). The overall 5-year survival rate was 42.3%. The survival curve of patients with a high HIF-$1{\alpha}$ expression was worse than that of patients with low-expression(p=0.002). High HIF-$1{\alpha}$ expression was independent unfavorable factors with a marginal significance in multivariate analysis performed by Cox regression. Conclusion: It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway, and high HIF-$1{\alpha}$ expression could be associated with lymph node metastasis and post operative poor prognosis in patients with non-small cell lung carcinoma.