scholarly journals OATP1B1 Plays an Important Role in the Transport and Treatment Efficacy of Sorafenib in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Jinhua Wen ◽  
Menghua Zhao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cell Viability ◽  
Rat Model ◽  
Hepg2 Cells ◽  
Genetic Mutations ◽  
Control Group ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Sorafenib Treatment ◽  
Apoptosis Rate

Background. Sorafenib is an anticancer drug used in the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma. It is a substrate for the human OATP1B1. This study is aimed at assessing the role of OATP1B1 in transportation and uptake of sorafenib in hepatocellular carcinoma and how OATP1B1 affects the pharmacodynamics of sorafenib in vitro and in vivo. Methods. Sorafenib transport was measured in HepG2, HepG2-OATP1B1 ∗ 1a, HepG2-OATP1B1 ∗ 1b, HepG2-OATP1B1 ∗ 15, LO2, LO2-OATP1B1 ∗ 1a, LO2-OATP1B1 ∗ 1b, and LO2-OATP1B1 ∗ 15 cells, as well as in HepG2 cells transfected with miR-148a mimics. The viability and apoptosis rate of cells treated with sorafenib were evaluated. A liver cancer rat model was established to explore the pharmacokinetics and pharmacodynamics of sorafenib after overexpression of Oatp2. Results. Changes in expression and genetic mutations of OATP1B1 significantly affected the uptake of sorafenib in HepG2 and LO2 transgenic cells, and the uptake of sorafenib was higher in HepG2 than LO2. Genetic mutations of OATP1B1 significantly affected the cell viability and apoptosis rate of HepG2 cells after sorafenib treatment. Compared to control group, the uptake of sorafenib in miR-148a mimic-transfected HepG2 cells was decreased, and the cell viability was increased. PCN significantly increased the expression of Oatp2 and affected the pharmacokinetics of sorafenib. Vascular endothelial growth factor levels and microvascular density in tumor-adjacent tissues decreased significantly, suggesting that increased Oatp2 expression improves the treatment effect of sorafenib in a rat model of liver cancer. Conclusions. OATP1B1 plays an important role in the pharmacokinetics and pharmacodynamics of sorafenib in hepatocellular carcinoma.

scholarly journals OATP1B1 Plays an Important Role in the Transport and Treatment Efficacy of Sorafenib in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
JinHua Wen ◽  
Menghua Zhao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cell Viability ◽  
Rat Model ◽  
Hepg2 Cells ◽  
Genetic Mutations ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Sorafenib Treatment ◽  
Apoptosis Rate

Abstract BackgroundSorafenib is an anticancer drug used in the treatment of unresectable hepatocellular carcinoma and advanced renal cell carcinoma. It is a substrate for the human OATP1B1. This study aimed to assess the role of OATP1B1 in transportation and uptake of sorafenib in hepatocellular carcinoma and how OATP1B1 affects the pharmacodynamics of sorafenib in vitro and in vivo.MethodsSorafenib transport was measured in HepG2, HepG2-OATP1B1*1a, HepG2-OATP1B1*1b, HepG2-OATP1B1*15, LO2, LO2-OATP1B1*1a, LO2-OATP1B1*1b, and LO2-OATP1B1*15 cells, as well as in HepG2 cells transfected with miR-148a mimics. The cell viability and apoptosis rate of cells treated with sorafenib were evaluated. A liver cancer rat model was established to explore the pharmacokinetics and pharmacodynamics of sorafenib after overexpression of Oatp2.ResultsChanges in expression and genetic mutations of OATP1B1 significantly affected the uptake of sorafenib in HepG2 and LO2 transgenic cells, and sorafenib uptake by HepG2 was higher than that by LO2. Genetic mutations of OATP1B1 significantly affected the cell viability and apoptosis rate of HepG2 cells after sorafenib treatment. Compared to control HepG2 cells, miR-148a mimic-transfected HepG2 cells had decreased sorafenib uptake. The inhibitory effect of sorafenib on cell growth was weakened. PCN significantly increased the expression of Oatp2 and affected the pharmacokinetics of sorafenib. Vascular endothelial growth factor levels and microvascular density in tumor-adjacent tissues decreased significantly, suggesting that increased Oatp2 expression improves the treatment effect of sorafenib in a rat model of liver cancer.ConclusionsOATP1B1 plays an important role in the pharmacokinetics and pharmacodynamics of sorafenib in hepatocellular carcinoma.

scholarly journals The Effect of Alpha Mangostin on Epithelial-Mesenchymal Transition on Human Hepatocellular Carcinoma HepG2 Cells Surviving Sorafenib via TGF-β/Smad Pathways

2020 ◽  
Vol 10 (4) ◽  
pp. 648-655
Author(s):  
Syarinta Adenina ◽  
Melva Louisa ◽  
Vivian Soetikno ◽  
Wawaimuli Arozal ◽  
Septelia Inawati Wanandi
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Hepg2 Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Sorafenib Treatment ◽  
Mesenchymal Transition ◽  
The Impact ◽  
Tgf Β1 ◽  
E Cadherin

Purpose : This study was intended to find out the impact of alpha mangostin administration on the epithelial-mesenchymal transition (EMT) markers and TGF-β/Smad pathways in hepatocellular carcinoma Hep-G2 cells surviving sorafenib. Methods: Hepatocellular carcinoma HepG2 cells were treated with sorafenib 10 μM. Cells surviving sorafenib treatment (HepG2surv) were then treated vehicle, sorafenib, alpha mangostin, or combination of sorafenib and alpha mangostin. Afterward, cells were observed for their morphology with an inverted microscope and counted for cell viability. The concentrations of transforming growth factor (TGF)-β1 in a culture medium were examined using ELISA. The mRNA expressions of TGF-β1, TGF-β1-receptor, Smad3, Smad7, E-cadherin, and vimentin were evaluated using quantitative reverse transcriptase–polymerase chain reaction. The protein level of E-cadherin was also determined using western blot analysis. Results: Treatment of alpha mangostin and sorafenib caused a significant decrease in the viability of sorafenib-surviving HepG2 cells versus control (both groups with P<0.05). Our study found that alpha mangostin treatment increased the expressions of vimentin (P<0.001 versus control). In contrast, alpha mangostin treatment tends to decrease the expressions of Smad7 and E-cadherin (both with P>0.05). In line with our findings, the expressions of TGF-β1 and Smad3 are significantly upregulated after alpha mangostin administration (both with P<0.05) versus control. Conclusion: Alpha mangostin reduced cell viability of sorafenib-surviving HepG2 cells; however, it also enhanced epithelial–mesenchymal transition markers by activating TGF-β/Smad pathways.

Assessment of miR-212 and Other Biomarkers in the Diagnosis and Treatment of HBV-infection-related Liver Diseases

2019 ◽  
Vol 20 (10) ◽  
pp. 785-798 ◽  
Author(s):  
Yigan Zhang ◽  
Huaze Xi ◽  
Xin Nie ◽  
Peng Zhang ◽  
Ning Lan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Liver Diseases ◽  
Meld Score ◽  
Hbv Infection ◽  
Expression Level ◽  
Control Group

Objective: Our study aims to detect the sensitivity of the new biomarker miR-212 existing in serum exosomes along with other hepatocellular carcinoma biomarkers such as AFP (alpha-fetoprotein), CA125 (carbohydrate antigen-ca125), and Hbx protein in the diagnosis of HBV-related liver diseases. We also aim to study the roles of these biomarkers in the progression of chronic hepatitis B and provide scientific data to show the clinical value of these biomarkers. Methods: We selected 200 patients with HBV-infection (58 cases of chronic hepatitis B, 47 cases of hepatocellular carcinoma, 30 cases of compensatory phase cirrhosis, and 65 cases of decompensatory phase cirrhosis), 31 patients with primary liver cancer without HBV infection, and 70 healthy individuals as the control group. The expression level of serum AFP and CA125 was detected with electrochemiluminescence immunoassay. The expression level of the Hbx protein was detected with ELISA. Meanwhile, the expression level of miR-212 in serum was analyzed with RT-qPCR. We collected patients’ clinical information following the Child-Pugh classification and MELD score criterion, and statistical analysis was made between the expression level of miR-212 and the collected clinical indexes. Lastly, we predicted the target genes of the miR-212 and its functions using bioinformatics methods such as cluster analysis and survival prediction. Results: Compared to the control group, the expression level of miR-212 in HBV infected patients was remarkably increased (P<0.05), especially between the HBV-infection Hepatocellular carcinoma group and the non-HBVinfection liver cancer group (P<0.05). The expression of miR-212 was increased in patients’ Child-Pugh classification, MELD score, and TNM staging. Moreover, the sensitivity and specificity of miR-212 were superior to AFP, CA125, and HBx protein. Conclusion: There is a linear relationship between disease progression and expression level of miR-212 in the serum of HBV infected patients. This demonstrates that miR-212 plays a significant role in liver diseases. miR-212 is expected to be a new biomarker used for the diagnosis and assessment of patients with HBV-infection-related liver diseases.

scholarly journals Possible Role of IRS-4 in the Origin of Multifocal Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2560
Author(s):  
Luis G. Guijarro ◽  
Patricia Sanmartin-Salinas ◽  
Eva Pérez-Cuevas ◽  
M. Val Toledo-Lobo ◽  
Jorge Monserrat ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepg2 Cells ◽  
Cellular Polarity ◽  
Ki 67 ◽  
Tissue Samples ◽  
Vitro Analysis ◽  
Tumoral Cells

New evidence suggests that insulin receptor substrate 4 (IRS-4) may play an important role in the promotion of tumoral growth. In this investigation, we have evaluated the role of IRS-4 in a pilot study performed on patients with liver cancer. We used immunohistochemistry to examine IRS-4 expression in biopsies of tumoral tissue from a cohort of 31 patient suffering of hepatocellular carcinoma (HCC). We simultaneously analyzed the expression of the cancer biomarkers PCNA, Ki-67, and pH3 in the same tissue samples. The in vitro analysis was conducted by studying the behavior of HepG2 cells following IRS-4 overexpression/silencing. IRS-4 was expressed mainly in the nuclei of tumoral cells from HCC patients. In contrast, in healthy cells involved in portal triads, canaliculi, and parenchymal tissue, IRS-4 was observed in the cytosol and the membrane. Nuclear IRS-4 in the tumoral region was found in 69.9 ± 3.2%, whereas in the surrounding healthy hepatocytes, nuclear IRS-4 was rarely observed. The percentage of tumoral cells that exhibited nuclear PCNA and Ki-67 were 52.1 ± 7%, 6.1 ± 1.1% and 1.3 ± 0.2%, respectively. Furthermore, we observed a significant positive linear correlation between nuclear IRS-4 and PCNA (r = 0.989; p < 0.001). However, when we correlated the nuclear expression of IRS-4 and Ki-67, we observed a significant positive curvilinear correlation (r = 0.758; p < 0.010). This allowed us to define two populations, (IRS-4 + Ki-67 ≤ 69%) and (IRS-4 + Ki-67 > 70%). The population with lower levels of IRS-4 and Ki-67 had a higher risk of suffering from multifocal liver cancer (OR = 16.66; CI = 1.68–164.8 (95%); p < 0.05). Immunoblot analyses showed that IRS-4 in normal human liver biopsies was lower than in HepG2, Huh7, and Chang cells. Treatment of HepG2 with IGF-1 and EGF induced IRS-4 translocation to the nucleus. Regulation of IRS-4 levels via HepG2 transfection experiments revealed the protein’s role in proliferation, cell migration, and cell-collagen adhesion. Nuclear IRS-4 is increased in the tumoral region of HCC. IRS-4 and Ki-67 levels are significantly correlated with the presence of multifocal HCC. Moreover, upregulation of IRS-4 in HepG2 cells induced proliferation by a β-catenin/Rb/cyclin D mechanism, whereas downregulation of IRS-4 caused a loss in cellular polarity and in its adherence to collagen as well as a gain in migratory and invasive capacities, probably via an integrin α2 and focal adhesion cascade (FAK) mechanism.

scholarly journals Synthesis, Characterization of Nano-β-Tricalcium Phosphate and the Inhibition on Hepatocellular Carcinoma Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Langlang Liu ◽  
Yanzeng Wu ◽  
Chao Xu ◽  
Suchun Yu ◽  
Xiaopei Wu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Particle Size ◽  
Cell Viability ◽  
Tricalcium Phosphate ◽  
Hepg2 Cells ◽  
Drug Carrier ◽  
Average Particle Size ◽  
Crystal Habit ◽  
Average Particle ◽  
Dependent Manner

It is difficult to synthesize nano-β-tricalcium phosphate (nano-β-TCP) owing to special crystal habit. The aim of this work was to synthesize nano-β-TCP using ethanol-water system and characterize it by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Malvern laser particle size analyzer, and transmission electron microscope (TEM). In addition, the inhibitory effect of nano-β-TCP on human hepatocellular carcinoma (HepG2) cells was also investigated using MTT assay, lactate dehydrogenase (LDH) leakage test, and 4′-6-diamidino-2-phenylindole (DAPI) staining. The results showed that negatively charged rod-like nano-β-TCP with about 55 nm in diameter and 120 nm in length was synthesized, and the average particle size of nano-β-TCP was 72.7 nm. The cell viability revealed that nano-β-TCP caused reduced cell viability of HepG2 cells in a time- and dose-dependent manner. These findings presented here may provide valuable reference data to guide the design of nano-β-TCP-based anticancer drug carrier and therapeutic systems in the future.

scholarly journals Therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma using contrast-enhanced ultrasound: Focusing on inter-scanner, and inter-operator reproducibility

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244304
Author(s):  
Hwaseong Ryu ◽  
Jung Hoon Kim ◽  
Seunghyun Lee ◽  
Joon Koo Han
Keyword(s):  
Hepatocellular Carcinoma ◽  
Targeted Therapy ◽  
Treatment Group ◽  
Rat Model ◽  
Therapeutic Response ◽  
Response Monitoring ◽  
Control Group ◽  
Rat Models ◽  
Significant Change ◽  
Operator Reproducibility

Purpose To assess therapeutic response monitoring after targeted therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) using CEUS with focusing on inter-scanner and inter-operator reproducibility. Materials and methods For reproducibility, CEUS was performed using two different US scanners by two operators in sixteen rat models of HCC. Using perfusion analysis software (VueBox ®), eleven parameters were collected, and intra-class correlation coefficient (ICC) was used to analyze reproducibility. Then seventeen rat models of HCC were divided into treatment group (n = 8, 30 mg/kg/day sorafenib for five days) and control group (n = 9). CEUS was performed at baseline and 14 days after first treatment, and changes of perfusion parameters were analyzed. Results In treatment group, CEUS perfusion parameters showed a significant change. The peak enhancement (PE, 2.50 x103±1.68 x103 vs 5.55x102±4.65x102, p = 0.010) and wash-in and wash out AUC (WiWoAUC, 1.07x105±6.48 x104 vs 2.65x104±2.25x104, p = 0.009) had significantly decreased two weeks after treatment. On the contrary, control group did not show a significant change, including PE (1.15 x103±7.53x102 vs 9.43x102± 7.81 x102, p = 0.632) and WiWoAUC (5.09 x104±3.25x104 vs 5.92 x104±3.20x104, p = 0.646). For reproducibility, the various degrees of inter-scanner reproducibility were from poor to good (ICC: <0.01–0.63). However, inter-operator reproducibility of important perfusion parameters, including WiAUC, WoAUC, and WiWoAUC, ranged from fair to excellent (ICC: 0.59–0.93) in a different scanner. Conclusion Our results suggest that CEUS is useful for assessment of the treatment response after targeted therapy and with fair to excellent inter-operator reproducibility.

Study of the antineoplastic effect of modulating apoptosis-related noncoding RNA in human hepatocellular carcinoma cell line (HepG2)

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mai Abdel Azeem Sherif ◽  
Emtiaz Abd-elkawy Ismail ◽  
Samar Kamal Kassim ◽  
Hanan Hussein Shehata ◽  
Marwa Ali Abdel Khalek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Noncoding Rna ◽  
Caspase 3 ◽  
Control Group ◽  
Antineoplastic Effect ◽  
And Control ◽  
Hcc Cells ◽  
Liver Tissues

Abstract MiR-421 is considered an important molecule that can prevent tumor growth. Bioinformatics analysis indicated that mRNA caspase-3 gene is a target gene of miR-421. The current study aimed to explore the functional role of miR-421 in hepatocellular carcinoma (HCC) and explore the interaction between miR-421 and caspase-3. To validate bioinformatics data, RT-qPCR was used to detect the expression of miR-421 and caspase-3 in 10 HCC tissues. The results showed miR-421 expression was significantly higher in HCC than non HCC liver tissues (P&lt;0.01), nevertheless caspase-3 gene expression was markedly lower in HCC than non HCC liver tissues (P&lt;0.01). Besides, miR-421 expression was negatively associated with caspase-3 expression. MiR-421 mimic and inhibitor was transfected into HCC cell lines (HepG2). Proliferation assay, showed that low-expression of miR-421 inhibited the proliferation of HCC cells. RT-qPCR was worked for detection the expression levels of miR-421 and caspase-3 in HepG2 cells before and after transfection. The results showed that miR-421 expression in HepG2 cells was significantly lower in miR-421 inhibitor transfected group than in mimic- transfected and control groups (Mock) (P≤ 0.05), and caspase-3 gene expression in HCC tissues was markedly higher in inhibitor transfected group than those transfected by mimic and control group (Mock) (P≤0.05). Thus, miR-421 inhibitor may inhibit the proliferation of HCC cells via over- expression of caspase-3.

Roles of Immune Cells in the Concurrence of Echinococcus Granulosus Infection and Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Aimaiti Yasen ◽  
Bo Ran ◽  
Maolin Wang ◽  
Guodong Lv ◽  
Renyong Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Immune Responses ◽  
Nk Cells ◽  
Echinococcus Granulosus ◽  
Immune Cells ◽  
Hepg2 Cells ◽  
Control Group ◽  
Cell Markers ◽  
Hepg2 Cell Lines

Abstract Background/aims: Immune cells are pivotal players in the immune responses against both parasitic infection and malignancies. Substantial evidence demonstrated that there may exist possible relationship between Echinococcus granulosus (E.granulosus) infection and hepatocellular carcinoma (HCC) development. Thus, this study aimed to observe crucial roles of immune cells in the formation of subcutaneous lesions after transplanting HepG2 cell lines with or without E.granulosus protoscoleces (PSCs).Methods: HepG2 cell lines were subcutaneously injected into nude mice in the control group. In the co-transplantation group, HepG2 cells were subcutaneously co-injected with high dosage of E.granulosus PSCs. From the 25th day of transplantation, volume of subcutaneous lesions was measured every four days, which were removed at the 37th day for further studies. Basic pathological and functional changes were observed. Moreover, expression of Ki67, Bal-2, Caspase3, α-smooth muscle actin (α-SMA), T cell markers (CD3, CD4, CD8), PD1/PD-L1, nature killer (NK) cell markers (CD16, CD56) were further detected by immunohistochemistry.Results: Subcutaneous lesions were gradually increased in volume and there occurred pathologically heterogeneous tumor cells, which were more significant in the co-transplantation group. Compared to the control group, expression of proliferation markers Ki67 and Bcl-2 was at higher levels in the co-transplantation group. Reversely, apoptotic marker Caspase3 was highly detected in the control group, suggesting promoting effects of E.granulosus PSCs on HCC development. Interestingly, subcutaneous lesions of the co-transplantation group were more functional in synthesizing and storing glycogen. Collagen and α-SMA+ cells were also at higher levels in the co-transplantation group than those in the control group. Most importantly, co-transplantation of HepG2 cells with E.granulosus PSCs led to significant increase in the expression of T cell markers (CD3, CD4 and CD8), immune inhibitory checkpoint PD1/PD-L1 and NK cells markers (CD16 and CD56). Conclusions: E.granulosus may have promoting effects on HCC development, which was closely associated with the immune responses of T cells and NK cells.

scholarly journals Antiproliferative and Apoptotic Effects of Cardamonin against Hepatocellular Carcinoma HepG2 Cells

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1757
Author(s):  
Nassrin A. Badroon ◽  
Nazia Abdul Majid ◽  
Mohammed A. Alshawsh
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Hepg2 Cells ◽  
Primary Liver Cancer ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Major Health Problem ◽  
Major Health ◽  
Late Apoptosis ◽  
Apoptotic Effects

Liver cancer is the sixth most common cancer in terms of incidence and the fourth in terms of mortality. Hepatocellular carcinoma (HCC) represents almost 90% of primary liver cancer and has become a major health problem globally. Cardamonin (CADMN) is a natural bioactive chalcone found in several edible plants such as cardamom and Alpinia species. Previous studies have shown that CADMN possesses anticancer activities against breast, lung, prostate and colorectal cancer. In the present study, the mechanisms underlying the anti-hepatocellular carcinoma effects of CADMN were investigated against HepG2 cells. The results demonstrated that CADMN has anti-proliferative effects and apoptotic action on HepG2 cells. CADMN showed potent cytotoxicity against HepG2 cells with an IC50 of 17.1 ± 0.592 μM at 72 h. Flow cytometry analysis demonstrated that CADMN arrests HepG2 cells in G1 phase and induces a significant increase in early and late apoptosis in a time-dependent manner. The mechanism by which CADMN induces apoptotic action was via activation of both extrinsic and intrinsic pathways. Moreover, the findings of this study showed the involvement of reactive oxygen species (ROS), which inhibit the NF-κB pathway and further enhance the apoptotic process. Together, our findings further support the potential anticancer activity of CADMN as an alternative therapeutic agent against HCC.

scholarly journals NFAT2 overexpression suppresses the malignancy of hepatocellular carcinoma through inducing Egr2 expression

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jian Wang ◽  
Yamin Zhang ◽  
Lei Liu ◽  
Zilin Cui ◽  
Rui Shi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Viability ◽  
Cell Fate ◽  
Hepg2 Cells ◽  
Annexin V ◽  
Activated T Cells ◽  
Cell Viability Assay ◽  
Invasion And Migration ◽  
Viability Assay ◽  
Cox 2

Abstract Background Nuclear factor of activated T cells 2 (NFAT2) has been reported to regulate the development and malignancy of few tumors. In this study, we aimed to explore the effect of NFAT2 expression on cell fate of HepG2 cell and its potential mechanisms. Methods Firstly, the pcDNA3.1-NFAT2 plasmid was transfected into HepG2 cells to construct NFAT2 overexpressed HepG2 cells. Then, the chemical count kit-8 cell viability assay, Annexin V-FITC apoptosis detection, EdU labeling proliferation detection, transwell and wound healing experiments were performed. The expression of Egr2 and FasL, and the phosphorylation of AKT and ERK, after ionomycin and PMA co-stimulation, was detected, while the Ca2+ mobilization stimulated by K+ solution was determined. At last, the mRNA and protein expression of NFAT2, Egr2, FasL, COX-2 and c-myc in carcinoma and adjacent tissues was investigated. Results The NFAT2 overexpression suppressed the cell viability, invasion and migration capabilities, and promoted apoptosis of HepG2 cells. NFAT2 overexpression induced the expression of Egr2 and FasL and suppressed the phosphorylation of AKT and ERK. The sensitivity and Ca2+ mobilization of HepG2 cells was also inhibited by NFAT2 overexpression. Compared with adjacent tissues, the carcinoma tissues expressed less NFAT2, Egr2, FasL and more COX-2 and c-myc. Conclusion The current study firstly suggested that NFAT2 suppressed the aggression and malignancy of HepG2 cells through inducing the expression of Egr2. The absence of NFAT2 and Egr2 in carcinoma tissues reminded us that NFAT2 may be a promising therapeutic target for hepatocellular carcinoma treatment.

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