scholarly journals Triptolide Inhibits the Biological Processes of HUVEC and HepG2 Cells via the Serine Palmitoyltransferase Long Chain Base Subunit 2/sphingosine-1-phosphate Signaling Pathway

Author(s):  
qinyou tan ◽  
shengnan zhu ◽  
mingfei zhu ◽  
lingyue huang ◽  
siyuan xu ◽  
...  

Abstract Background: Hepatocellular carcinoma is a cancer that has a high incidence in men, and its incidence is increasing year by year. Studies show that angiogenesis plays an important role in the formation of tumors, not only providing nutrients to tumor cells, but also closely related to tumor growth and metastasis. So, how to find new anti-vascular and anti-tumor targets for the pathogenesis of liver cancer is a key issue that needs to be resolved.Methods: After treating Human umbilical vein endothelial cells (HUVEC) and HepG2 cells with different concentrations of triptolide (TP), the relationship between TP's anti-vascular and anti-tumor activities and sphingolipids was investigated respectively. Then, the three-dimensional co-culture model was used to explore the correlation between HUVEC and HepG2 cells, and to find the relationship between it and sphingolipids.Results: This study explored the effects of TP on the proliferation, migration, adhesion and tube formation of HUVEC cells, as well as the effects on the proliferation, migration and invasion of HepG2 cells. And through the PCR Array assay to screen the changes of related sphingolipid genes, it was found that serine palmitoyltransferase long chain base subunit 2 (SPTLC2) was most likely to be related to the effect of TP. In further transfection experiments, it was found that down-regulation of SPTLC2 can inhibit the proliferation, migration, adhesion and tube formation of HUVEC cells, and down-regulation of SPTLC2 can also inhibit the proliferation, migration and invasion of HepG2 cells. The up-regulation of SPTLC2 has opposite effects in these two cell lines. In the three-dimensional co-culture model of HUVEC and HepG2 cells, it was found for the first time that HUVEC cells can promote the biological process of HepG2 cells. It was found through enzyme linked immunosorbent assay (ELISA) and western blot experiments that it may be achieved through the sphingosine-1-phosphate (S1P)/S1P receptors (S1PRs) pathway. Finally, we found that the promotion effect of HUVEC cells on HepG2 cells was significantly inhibited after HUVEC cells were treated with TP.Conclusions: These data confirmed that the level of SPTLC2 may be related to the anti-vascular and anti-tumor effects of TP. The data also showed that there was a correlation between the viability of HepG2 cells and HUVEC cells, which may be related to the expression of S1P/S1PRS. Ultimately, these data may help discover new anti-tumor targets.

2021 ◽  
Author(s):  
Qinyou Tan ◽  
Shengnan Zhu ◽  
Mingfei Zhu ◽  
Lingyue Huang ◽  
Siyuan Xu ◽  
...  

Abstract Background: Hepatocellular carcinoma is a cancer that has a high incidence in men, and its incidence is increasing year by year. Studies show that angiogenesis plays an important role in the formation of tumors, not only providing nutrients to tumor cells, but also closely related to tumor growth and metastasis. So, how to find new anti-vascular and anti-tumor targets for the pathogenesis of liver cancer is a key issue that needs to be resolved. Methods: After treating HUVEC and HepG2 cells with different concentrations of TP, the relationship between TP's anti-vascular and anti-tumor activities and sphingolipids was investigated respectively. Then, the three-dimensional co-culture model was used to explore the correlation between HUVEC and HepG2 cells, and to find the relationship between it and sphingolipids. Results: TP can inhibit the tube formation process of HUVEC cells. Through PCR Array, PCR and Western Blot experiments, it is found that it may achieve this effect by down-regulating SPTLC2. TP can also inhibit the proliferation, migration and invasion of HepG2 cells through the same mechanism. In the three-dimensional co-culture model of HUVEC and HepG2 cells, it was found for the first time that HUVEC can promote the biological process of HepG2 cells. It was found through ELISA and Western Blot experiments that it may be achieved through the S1P/S1PRS pathway, and TP was found in the dosing experiment. It can significantly inhibit the induction of HUVEC on HepG2 cells. Conclusions: These data confirm that the level of SPTLC2 may be related to the anti-vascular and anti-tumor effects of TP. The data also showed that there is a correlation between the viability of HepG2 cells and HUVEC cells, which may be related to the expression of S1P/S1PRS. Ultimately, these data may help discover new anti-tumor targets.


Author(s):  
Bin Xiao ◽  
Dongjing Lin ◽  
Xuan Zhang ◽  
Meilan Zhang ◽  
Xuewu Zhang

TTF1-NP(5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showedits anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 hepatoma cells and HepG2 cells-induced hepatocarcinoma (HCC) in nude mouse model. Here we demonstrated that TTF1-NP inhibits tube formation of HUVECs and HepG2 cell migration and invasion, and inhibits tumor growth in nude mice implanted with HepG2 cells through the downregulation of STAT3 protein and activation, along with VEGF, KDR, bFGF, MMP2 and MMP9 levels. We further revealed that TTF1-NP decreased the DNA-binding capacity of STAT3. Together our results provide a mechanism by which TTF1-NP suppresses cancer cell migration, invasion and angiogenesis through the action of STAT3 and suggests TTF1-NP as a potential therapy for hepatocellular cancer treatment.


2018 ◽  
Vol 18 (7) ◽  
pp. 1025-1031
Author(s):  
Cheng Luo ◽  
Di Wu ◽  
Meiling Chen ◽  
Wenhua Miao ◽  
Changfeng Xue ◽  
...  

Background: Different saponins from herbs have been used as tonic or functional foods, and for treatment of various diseases including cancers. Although clinical data has supported the function of these saponins, their underlying molecular mechanisms have not been well defined. Methods: With the simulated hypoxia created by 8 hours of Cu++ exposure and following 24 hour incubation with different concentration of saponins in HepG2 cells for MTT assay, migration and invasion assays, and for RT-PCR, and with each group of cells for immunofluorescence observation by confocal microscopy. Results: ZC-4 had the highest rate of inhibition of cell proliferation by MTT assay, and the highest inhibition of migration rate by in vitro scratch assay, while ZC-3 had the highest inhibition of invasion ratio by transwell assay. Under the same simulated hypoxia, the molecular mechanism of saponin function was conducted by measuring the gene expression of Hypoxia Inducible Factor (HIF)-1α through RT-PCR, in which ZC-3 showed a potent inhibition of gene HIF-1α. For the protein expression by immunofluorescence staining with confocal microscopy, HIF-1α was also inhibited by saponins, with the most potent one being ZC-4 after eight hours’ relatively hypoxia incubation. Conclusion: Saponins ZC-4 and ZC-3 have the potential to reduce HepG2 cell proliferation, migration and invasion caused by hypoxia through effectively inhibiting the gene and protein expression of HIF-1α directly and as antioxidant indirectly


Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 841
Author(s):  
Yuzhen Jin ◽  
Huang Zhou ◽  
Linhang Zhu ◽  
Zeqing Li

A three-dimensional numerical study of a single droplet splashing vertically on a liquid film is presented. The numerical method is based on the finite volume method (FVM) of Navier–Stokes equations coupled with the volume of fluid (VOF) method, and the adaptive local mesh refinement technology is adopted. It enables the liquid–gas interface to be tracked more accurately, and to be less computationally expensive. The relationship between the diameter of the free rim, the height of the crown with different numbers of collision Weber, and the thickness of the liquid film is explored. The results indicate that the crown height increases as the Weber number increases, and the diameter of the crown rim is inversely proportional to the collision Weber number. It can also be concluded that the dimensionless height of the crown decreases with the increase in the thickness of the dimensionless liquid film, which has little effect on the diameter of the crown rim during its growth.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tokuji Tsuji ◽  
Shin-ya Morita ◽  
Yoshinobu Nakamura ◽  
Yoshito Ikeda ◽  
Taiho Kambe ◽  
...  

AbstractThe human hepatoblastoma cell line, HepG2, has been used for investigating a wide variety of physiological and pathophysiological processes. However, less information is available about the phospholipid metabolism in HepG2 cells. In the present report, to clarify the relationship between cell growth and phospholipid metabolism in HepG2 cells, we examined the phospholipid class compositions of the cells and their intracellular organelles by using enzymatic fluorometric methods. In HepG2 cells, the ratios of all phospholipid classes, but not the ratio of cholesterol, markedly changed with cell growth. Of note, depending on cell growth, the phosphatidic acid (PA) ratio increased and phosphatidylcholine (PC) ratio decreased in the nuclear membranes, the sphingomyelin (SM) ratio increased in the microsomal membranes, and the phosphatidylethanolamine (PE) ratio increased and the phosphatidylserine (PS) ratio decreased in the mitochondrial membranes. Moreover, the mRNA expression levels of enzymes related to PC, PE, PS, PA, SM and cardiolipin syntheses changed during cell growth. We suggest that the phospholipid class compositions of organellar membranes are tightly regulated by cell growth. These findings provide a basis for future investigations of cancer cell growth and lipid metabolism.


Atmosphere ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 873
Author(s):  
Dandan Xia ◽  
Liming Dai ◽  
Li Lin ◽  
Huaifeng Wang ◽  
Haitao Hu

The field measurement was conducted to observe the wind field data of West Pacific typhoon “Maria” in this research. With the application of ultrasonic anemometers installed in different heights (10 m, 80 m, 100 m) of the tower, the three dimensional wind speed data of typhoon “Maria” was acquired. In addition, vane-type anemometers were installed to validate the accuracy of the wind data from ultrasonic anemometers. Wind characteristics such as the mean wind profile, turbulence intensity, integral length scale, and wind spectrum are studied in detail using the collected wind data. The relationship between the gust factor and turbulence intensity was also studied and compared with the existing literature to demonstrate the characteristics of Maria. The statistical characteristics of the turbulence intensity and gust factor are presented. The corresponding conclusion remarks are expected to provide a useful reference for designing wind-resistant buildings and structures.


Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 739
Author(s):  
Ulvi K. Gürsoy ◽  
Krista Salli ◽  
Eva Söderling ◽  
Mervi Gürsoy ◽  
Johanna Hirvonen ◽  
...  

Human milk oligosaccharides (HMOs), the third largest solid fraction in human milk, can modulate inflammation through Toll-like receptor signaling, but little is known about their immunomodulatory potential in the oral cavity. In this study, we determined whether the HMOs 2’-fucosyllactose (2’-FL) and 3-fucosyllactose (3-FL) regulate human-beta defensin (hBD)-2 and -3, cathelicidin (hCAP18/LL-37), and cytokine responses in human gingival cells using a three-dimensional oral mucosal culture model. The model was incubated with 0.1% or 1% 2’-FL and 3-FL, alone and in combination, for 5 or 24 h, and hBD-2, hBD-3, and hCAP18/LL-37 were analyzed by immunohistochemistry. The expression profiles of interleukin (IL)-1, IL-1RA, IL-8, and monocyte chemoattractant protein (MCP)-1 were determined by LUMINEX immunoassay. The combination of 1% 2’-FL and 1% 3-FL, and 1% 3-FL alone, for 24 h upregulated hBD-2 protein expression significantly (p < 0.001 and p = 0.016, respectively). No changes in the other antimicrobial peptides or proinflammatory cytokines were observed. Thus, 3-FL, alone and in combination with 2´-FL, stimulates oral mucosal secretion of hBD-2, without effecting a proinflammatory response when studied in an oral mucosal culture model.


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