Effects of Liver Cancer Drugs on Cellular Energy Metabolism in Hepatocellular Carcinoma Cells

Background: Hepatocellular carcinoma is one of the most common malignant tumors found all over the globe. Despite advances in surgery and chemotherapy, the five-year survival rate of patients with hepatocellular carcinoma is still low. It is known that the proliferation of hepatocellular carcinoma cells is closely related to the occurrence, development and prog- nosis of hepatocellular carcinoma. The present work investigates the expression of microRNA-489 (miR-489) in human hepatocellular carcinoma cells and its effect on the biological behavior of human hepatocellular carcinoma cells. Methods: The expression of miR-489 by fluorescence quantitative PCR detection in 30 patients with hepatoblastoma of liver cancer tissues and adjacent tissues was studied. Also, the determination of hepatoblastoma in four cell lines with differ- ent metastatic potential (HR8348, HCT116, HT29 and HEPG2) and the expression of miR-489 during miR-489 simulation process was studied. MTT assay, flow cytometry and Western blot analysis were performed to know the cell proliferation to detect the changes in cell cycle, apoptosis of cells, and SOX4 gene expression respectively. Results: RT-PCR results showed that the cells compared with pre-cancerous tissue, the expression level of miR-489 in hepatocellular carcinoma tissues than in adjacent tissue significantly decreased (P<0.05), and with liver cancer cell metastasis increased (P<0.05); analogue transfection constructed miR-489 overexpressing HEPG2 cell line by microRNA. MTT results showed that miR-489 can inhibit the proliferation of HEPG2 cells, the differences were statistically significant (P<0.05); flow cytometry results showed that miR-489 mimics was transfected into HEPG2 cells at 48 hours had no significant effect on cell cycle distribution (P > 0.05); but miR-489 expression could induce apoptosis, compared with the control group, the apoptosis of miR-489 mimics was significantly increased and the difference was statistically significant (P < 0.05). Conclusion: In conclusion, miR-489 can significantly inhibit the occurrence and development of hepatocellular carcinoma cells. The mechanism may be down regulated by the expression of SOX4 and inhibit cell proliferation. Further this study showed that the tumor cells SOX4 gene as a regulatory factor target the genes of miR-489 in hepatocellular carcinoma. Keywords: Hepatocellular carcinoma; mircroRNA-489; SOX4; apoptosis.

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Construction of Lycetin Nanocarriers and Its Effect on the Proliferation and Apoptosis of Hepatocellular Carcinoma Cells by Regulating Nuclear Factor E2 Related Factor/Antioxidant Response Element Pathway

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2021.18630 ◽

2021 ◽

Vol 21 (2) ◽

pp. 1054-1060

Author(s):

Ming Jiang ◽

Jing Jin ◽

Xiaohui Ye ◽

Jing Wang ◽

Hongbo Shen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Cancer Cells ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells ◽

Liver Cancer Cells ◽

Human Liver Cancer ◽

Human Liver Cancer Cells ◽

Targeting Effect ◽

Human Hepatocellular Carcinoma Cells

This article explores the role of lysin nanocarriers in inducing apoptosis of human hepatocellular carcinoma cells and the possible molecular mechanisms. Cytotoxicity tests were performed in human fibroblast cell line MRC-5. Anti-cancer activity was tested in liver cancer cell lines HepG2 and HCCLM3. The results show that nanocarriers have a targeting effect on cancer cells, have high safety, and are good delivery vehicles for drugs. In this paper, the stability of lycopene and its degradation in aqueous solutions at different temperatures were studied, and the structure and mechanism of degradation products were determined. A new type of mesoporous silica nanocarrier was synthesized as a delivery carrier of lysin and its derivatives, which has a targeting effect on cancer cells and has a slow-release effect. Surface modification can improve circulation time and stability for future resistance in vivo. The cancer experiment laid the foundation. The results showed that the lysin nanocarriers inhibited the proliferation of HepG2 and HCCLM3 human liver cancer cells in a dependent manner. After the lysin nanocarriers acted on HepG2 human hepatocellular carcinoma cells for 48 h, the cell apoptosis rate was significantly increased by flow cytometry analysis. The carrier can significantly increase the levels of reactive oxygen species and malondialdehyde, and reduce the content of reduced glutathione and superoxide dismutase. At the same time, the lysin nanocarrier can down-regulate the expression of Nrf2 and HO-1 proteins, and inhibit the occurrence of Nrf2 Nuclear displacement. The lycopene nanocarrier inhibits the proliferation of HepG2, HCCLM3 human liver cancer cells, induces apoptosis, regulates the oxidative stress response in the cell, and regulates the Nrf2/AREE antioxidant signaling pathway, thereby promoting tumor cell apoptosis.

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The influence of TLR4 agonist lipopolysaccharides on hepatocellular carcinoma cells and the feasibility of its application in treating liver cancer

OncoTargets and Therapy ◽

10.2147/ott.s86536 ◽

2015 ◽

pp. 2215 ◽

Cited By ~ 1

Author(s):

Zujiang Yu ◽

Junsheng Gu ◽

Ranran Sun ◽

Shen Shen

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells ◽

Tlr4 Agonist

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Effect of borrelidin on hepatocellular carcinoma cells in vitro and in vivo

RSC Advances ◽

10.1039/c7ra08290h ◽

2017 ◽

Vol 7 (70) ◽

pp. 44401-44409 ◽

Cited By ~ 5

Author(s):

Xiaoxiao Gao ◽

Yi Jiang ◽

Li Han ◽

Xiu Chen ◽

Caijuan Hu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Common Type ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells ◽

High Prevalence

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high prevalence and mortality.

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Energy metabolism determines the sensitivity of human hepatocellular carcinoma cells to mitochondrial inhibitors and biguanide drugs

Oncology Reports ◽

10.3892/or.2015.4092 ◽

2015 ◽

Vol 34 (3) ◽

pp. 1620-1628 ◽

Cited By ~ 8

Author(s):

CHIA-CHI HSU ◽

LING-CHIA WU ◽

CHENG-YUAN HSIA ◽

PEN-HUI YIN ◽

CHIN-WEN CHI ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Energy Metabolism ◽

Carcinoma Cells ◽

Human Hepatocellular Carcinoma ◽

Hepatocellular Carcinoma Cells ◽

Mitochondrial Inhibitors ◽

Human Hepatocellular Carcinoma Cells

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Effect of sorafenib on the energy metabolism of hepatocellular carcinoma cells

European Journal of Pharmacology ◽

10.1016/j.ejphar.2011.08.038 ◽

2011 ◽

Vol 670 (1) ◽

pp. 39-43 ◽

Cited By ~ 19

Author(s):

Luigi Fiume ◽

Marcella Manerba ◽

Marina Vettraino ◽

Giuseppina Di Stefano

Keyword(s):

Hepatocellular Carcinoma ◽

Energy Metabolism ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells

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Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells

10.21203/rs.3.rs-153445/v1 ◽

2021 ◽

Author(s):

Bingxin Li ◽

Maojun Zhou ◽

Jue Wang ◽

Hongjuan Xu ◽

Manyi Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Drug Resistance ◽

Liver Cancer ◽

Nuclear Translocation ◽

Carcinoma Cells ◽

Liver Carcinoma ◽

Hepatocellular Carcinoma Cells ◽

Extracellular Signal Regulated Kinase ◽

Apoptotic Protein ◽

Extracellular Signal

Abstract Background This research aims to examine the mechanism of glycochenodeoxycholate (GCDA)-mediated survival and drug-resistance in hepatocellular carcinoma cells (HCC). Extracellular signal-regulated kinase 1/2 (ERK1/2) were extensively expressed in liver cancer cells.Methods GCDA-induced survival of human liver carcinoma cells and chemoresistance was determined by CCK8 and flow cytometry, respectively. Functional of ERK1/2 and interaction of Bcl-2 family members was determined in western blot and immunofluorescence.Results Silencing ERK1/2 by RNA interference suppressed GCDA-stimulated survival and promoted apoptosis. Furthermore, phosphorylation of endogenous ERK1/2 could be potently stimulated by GCDA in combination with enhanced chemoresistance in QGY-7703 hepatocellular carcinoma cells. And such GCDA-mediated proliferation and chemoresistance could be impaired by PD98059, who acts as an inhibitor to block phosphorylation of ERK1/2. Mechanistically, PD98059 was able to potently suppress GCDA-stimulated nuclear aggregation of ERK1/2 and p-ERK1/2, up-regulation of pro-survival protein Mcl-1 and decrease of pro-apoptotic protein Bim.Conclusions Our work verified the function of ERK1/2 in GCDA-induced chemoresistance in hepatocellular carcinoma cells. Disruption of ERK1/2 by blocking phosphorylation or nuclear translocation may put forward new methods for treating of GCDA-related proliferation and drug-resistance in liver cancer.

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Suppressing ERK Pathway Impairs Glycochenodeoxycholate-Mediated Survival and Drug-Resistance in Hepatocellular Carcinoma Cells

Frontiers in Oncology ◽

10.3389/fonc.2021.663944 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bingxin Li ◽

Maojun Zhou ◽

Jue Wang ◽

Hongjuan Xu ◽

Manyi Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Drug Resistance ◽

Liver Cancer ◽

Nuclear Translocation ◽

Carcinoma Cells ◽

Hepatocellular Carcinoma Cells ◽

Extracellular Signal Regulated Kinase ◽

New Methods ◽

Apoptotic Protein ◽

Extracellular Signal

Glycochenodeoxycholate (GCDA), a toxic component in bile salts, is involved in carcinogenesis of gastrointestinal tumors. The objective of this research was to study the function of ERK1/2 in the GCDA-mediated survival and drug-resistance in hepatocellular carcinoma cells (HCCs). Firstly, extracellular signal-regulated kinase 1/2 (ERK1/2) was detected extensively expressed in liver cancer cells, and silencing ERK1/2 by RNA interference could suppress GCDA-stimulated survival and promote apoptosis. Furthermore, phosphorylation of endogenous ERK1/2 could be potently stimulated by GCDA in combination with enhanced chemoresistance in QGY-7703 hepatocellular carcinoma cells. The GCDA-mediated proliferation and chemoresistance could be impaired by PD98059, which acted as an inhibitor to block the phosphorylation of ERK1/2. Mechanistically, PD98059 was able to potently suppress GCDA-stimulated nuclear aggregation of ERK1/2 and p-ERK1/2, upregulate pro-survival protein Mcl-1 and downregulate pro-apoptotic protein Bim. The results of this study indicated that disruption of ERK1/2 by blocking phosphorylation or nuclear translocation may put forward new methods for solving the problem of GCDA-related proliferation and drug-resistance in liver cancer treatment.

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