Effects of fibromodulin protein expression on NFkB and TGFβ signaling pathways in liver cancer cells

Abstract Objectives Visfatin is found in adipose tissue and is referred to as nicotinamide phosphoribosyltransferase (Nampt). Visfatin has anti-apoptotic, proliferative, and metastatic properties and may mediate its effects via ERK and PI3K/Akt signaling. Studies have yet to determine whether inhibition of kinase signaling will suppress visfatin-induced liver cancer. The purpose of this study was to determine which signaling pathways visfatin may promote liver cancer progression. Methods HepG2 and SNU-449 liver cancer cells were exposed to visfatin with or without ERK or PI3K/Akt inhibitor, or both inhibitors combined. These processes that were assessed: proliferation, reactive oxygen species (ROS), lipogenesis, invasion, and matrix metalloproteinase (MMP). Results Inhibition of PI3K/Akt and combination of inhibitors suppressed visfatin-induced viability. ERK inhibition in HepG2 cells decreased visfatin-induced proliferation. ERK inhibitor alone or in combination with PI3K inhibitors effectively suppressed MMP-9 secretion and invasion in liver cancer cells. PI3K and ERK inhibition and PI3K inhibition alone blocked visfatin’s ROS production in SNU-449 cells. These results corresponded with a decrease in phosphorylated Akt and ERK, β-catenin, and fatty acid synthase. Conclusions Akt and ERK inhibition differentially regulated physiological changes in liver cancer cells. Inhibition of Akt and ERK signaling pathways suppressed visfatin-induced invasion, viability, MMP-9 activation, and ROS production.

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Differential effects of interferon alpha-2b and beta on the signaling pathways in human liver cancer cells

Journal of Gastroenterology ◽

10.1007/s00535-005-1616-x ◽

2005 ◽

Vol 40 (7) ◽

pp. 722-732 ◽

Cited By ~ 13

Author(s):

Kazuya Matsumoto ◽

Jun-ichi Okano ◽

Yoshikazu Murawaki

Keyword(s):

Liver Cancer ◽

Cancer Cells ◽

Signaling Pathways ◽

Interferon Alpha ◽

Human Liver ◽

Differential Effects ◽

Liver Cancer Cells ◽

Interferon Alpha 2B ◽

Human Liver Cancer ◽

Human Liver Cancer Cells

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NU7441 Enhances the Radiosensitivity of Liver Cancer Cells

Cellular Physiology and Biochemistry ◽

10.1159/000445551 ◽

2016 ◽

Vol 38 (5) ◽

pp. 1897-1905 ◽

Cited By ~ 10

Author(s):

Chuanjie Yang ◽

Quanxu Wang ◽

Xiaodan Liu ◽

Xiulian Cheng ◽

Xiaoyu Jiang ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Dna Repair ◽

Liver Cancer ◽

Protein Expression ◽

Cancer Cells ◽

Hepg2 Cells ◽

Specific Inhibitor ◽

Cell Counting ◽

Liver Cancer Cells

Objective: Radiation therapy, one of the major treatments for liver cancer, causes DNA damage and cell death. Since the liver cancer cells have a strong capacity to repair irradiative injury, new medicines to enhance this treatment are urgently required. In this study, we investigated the effect of NU7441, a synthetic small-molecule compound, as a specific inhibitor of DNA-dependent protein kinase (DNA-PK) in radiosensitization of hepatocellular carcinoma HepG2 cells. Methods: Cell Counting Kit-8 (CCK-8) was first used to evaluate the proliferation of HepG2 cells under NU7441 treatment. SDS-PAGE and Western blot were then performed to study the protein expression leading to the DNA damage repair. Further, neutral single cell gel electrophoresis and immunofluorescence assay were carried out to assess DNA repair. Finally, flow cytometry was implemented to examine the changes in cell cycle. Results: NU7441 reduced the CCK-8 counts in the HepG2 culture, further enhanced 60Coγ radiation injury to HepG2 cells, which was manifested by decreasing the DNA-PKcs (S2056) protein expression, increasing γH2AX foci number, prolonging the tail moment of the comet cells, and inducing cell cycle arrest at G2/M phase. Conclusion: NU7441 inhibited the growth of liver cancer cells, enhanced the radiosensitization of these cancer cells by interfering with the DNA repair and cell cycle checkpoint. These data implicate NU7441 as a potential radiotherapy sensitizer for the treatment of liver cancer.

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Sedanolide induces autophagy through the PI3K, p53 and NF-κB signaling pathways in human liver cancer cells

International Journal of Oncology ◽

10.3892/ijo.2015.3206 ◽

2015 ◽

Vol 47 (6) ◽

pp. 2240-2246 ◽

Cited By ~ 8

Author(s):

SHU-LING HSIEH ◽

CHI-TSAI CHEN ◽

JYH-JYE WANG ◽

YU-HAO KUO ◽

CHIEN-CHUN LI ◽

...

Keyword(s):

Liver Cancer ◽

Cancer Cells ◽

Signaling Pathways ◽

Human Liver ◽

Liver Cancer Cells ◽

Human Liver Cancer ◽

Human Liver Cancer Cells

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Amarogentin Induces Apoptosis of Liver Cancer Cells via Upregulation of p53 and Downregulation of Human Telomerase Reverse Transcriptase in Mice

Technology in Cancer Research & Treatment ◽

10.1177/1533034616657976 ◽

2016 ◽

Vol 16 (5) ◽

pp. 546-558 ◽

Cited By ~ 8

Author(s):

Chun Huang ◽

Runqin Li ◽

Yinglin Zhang ◽

Jianping Gong

Keyword(s):

Liver Cancer ◽

Protein Expression ◽

Reverse Transcriptase ◽

Cancer Cells ◽

Cell Apoptosis ◽

Telomerase Reverse Transcriptase ◽

Human Telomerase Reverse Transcriptase ◽

Liver Cancer Cells ◽

Gene And Protein Expression ◽

Human Telomerase

Background and Objective: Amarogentin has been reported to have a preventive effect on liver cancer via inducing cancer cell apoptosis. We attempted to elucidate the roles of p53-associated apoptosis pathways in the chemopreventive mechanism of amarogentin. The findings of this study will facilitate the development of a novel supplementary strategy for the treatment of liver cancer. Materials and Methods: The purity of amarogentin was assessed by high-performance liquid chromatography. The inhibitory ratios of the liver cell lines were determined using a Cell Counting Kit-8 following treatment with a gradient concentration of amarogentin. Cell apoptosis was detected by flow cytometry using annexin V-fluorescein isothiocyanate/propidium iodide kits. The gene and protein expression of p53-associated molecules, such as Akt, human telomerase reverse transcriptase, RelA, and p38, was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical staining in liver cancer cells and mouse tumor tissues after treatment with amarogentin. Results: The inhibitory effect of amarogentin on cell proliferation was more obvious in liver cancer cells, and amarogentin was more likely to induce the apoptosis of liver cancer cells than that of normal liver cells. The gene and protein expression levels of Akt, RelA, and human telomerase reverse transcriptase were markedly higher in the control group than in the preventive group and treatment groups. Only the expression of human telomerase reverse transcriptase was downregulated, accompanied by the upregulation of p53. Conclusion: The results of our study suggest that amarogentin promotes apoptosis of liver cancer cells by the upregulation of p53 and downregulation of human telomerase reverse transcriptase and prevents the malignant transformation of these cells.

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